天然产物主题快报 2009-06-02
Natural Products Research Express 090602
Part I Latest Original Research Articles
Angewantle Chemie International
1. Insects: True Pioneers in Anti-Infective Therapy and What We Can Learn from Them (p
NA)
Helge B. Bode
Published Online: Jun 30 2009 2:53PM DOI: 10.1002/anie.200902152
Abstract: Candicidin D is a potent natural product that was recently re-isolated from bacterial
insect symbionts. Some insects cultivate the producing bacteria in specialized organs in order to
fight pathogens. Besides the identification of new natural products for human use, these findings
have also implications for our unrstanding of resistance development and drug discovery strategies
in general.
Pdf see 090702a-1
2. The True Structures of the Vannusals, Part 2: Total Synthesis and Revised Structure of
Vannusal B (p NA)
K. C. Nicolaou, Adrian Ortiz, Hongjun Zhang Published Online: Jun 27 2009 3:28AM
DOI: 10.1002/anie.200902029
Abstract: The intriguing vannusal chemical detective saga based on an interplay between
chemical synthesis and NMR spectroscopy finally led to the revision of the structure of vannusal
B from 1 to 2 through the total synthesis of the latter.
Pdf see 090702a-2
3. Total Synthesis of Celogentin C (p NA)
Bing Ma, Dmitry N. Litvinov, Liwen He, Biplab Banerjee, Steven L. Castle
Published Online: Jun 24 2009 10:05AM DOI: 10.1002/anie.200902425
Abstract: Crazy cross-links: The first total synthesis of a member of the celogentin/moroidin
family of antimitotic bicyclic peptides features a Knoevenagel condensation-radical conjugate
addition sequence to install the Leu Trp cross-link and an indole-imidazole oxidative coupling
to fashion the Trp His cross-link (see structure).
Pdf see 090702a-3
4. Asymmetric Total Synthesis of Soraphen A: A Flexible Alkyne Strategy (p NA)
Barry M. Trost, Joshua D. Sieber, Wei Qian, Rajiv Dhawan, Zachary T. Ball
Published Online: Jun 24 2009 10:05AM DOI: 10.1002/anie.200901907
Abstract: A triple bond bonanza: The alkyne functional group can be a valuable handle for
organic synthesis because the alkyne unit can function both as a nucleophile or as an electrophile
when activated with an appropriate metal catalyst. This dual nature of the alkyne moiety has been
exploitated for the concise total synthesis of the natural product soraphen A (see retrosynthesis;
PMB=para-methoxybenzyl, TBS=tert-butyldimethylsilyl).
Pdf see 090702a-4
5. Stereochemistry Determination by Powder X-Ray Diffraction Analysis and NMR
Spectroscopy Residual Dipolar Couplings (p NA)
Manuela E. García, Silvina Pagola, Armando Navarro-Vázquez, Damilola D. Phillips, Chakicherla
Gayathri, Henry Krakauer, Peter W. Stephens, Viviana E. Nicotra, Roberto R. Gil
Published Online: Jun 24 2009 10:05AMDOI: 10.1002/anie.200900760
Abstract: A matter of technique: For a new steroidal lactol, jaborosalactol 24 (1), isolated from
Jaborosa parviflora, NMR spectroscopy residual dipolar couplings and powder X-ray diffraction
analysis independently gave the same stereochemistry at C23-C26. Conventional NMR
spectroscopic techniques, such as NOE and 3J coupling-constant analysis failed to unambiguously
determine this stereochemistry.
Pdf see 090702a-5
6. Total Synthesis of Cyathin A3 and Cyathin B2 (p NA)
Keunho Kim, Jin Kun Cha Published Online: Jun 18 2009 8:18AM DOI: 10.1002/anie.200901669
Abstract: A stereoselective synthesis of cyathin A3 and cyathin B2 has been achieved by a
Prins-type reaction of a cycloalkenyl cyclopropanol. Particularly noteworthy is the use of a
spirocyclobutanone moiety as a convenient scaffold for an efficient ring-closing metathesis to
stereoselectively construct a suitably functionalized seven-membered ring (see scheme).
Pdf see 090702a-6/090703a-1
Bioorganic & Medicinal Chemistry Letters
7. C29-Sterols with a cyclopropane ring at C-25 and 26 from the Vietnamese marine sponge
Ianthella sp. and their anticancer properties
In Press, Accepted Manuscript, Available online 2 July 2009
Nguyen Huu Tung, Chau Van Minh, Tran Thu Ha, Phan Van Kiem, Hoang Thanh Huong, Nguyen
Tien Dat, Nguyen Xuan Nhiem, Bui Huu Tai, Jae-Hee Hyun, Hee-Kyoung Kang, Young Ho Kim
Abstract: Two new C29 sterols with a cyclopropane ring at C-25 and C-26, petrosterol-3,6-dione (1)
and 5α,6α-epoxy-petrosterol (2), along with petrosterol (3), were isolated from the Vietnamese
marine sponge Ianthella sp. The structures of the new compounds were elucidated by
comprehensive spectroscopic analyses. Compounds 1−3 showed cytotoxic activities on A549,
HL-60, MCF-7, SK-OV-3, and U937 cancer cell lines with IC50 in the range of 8.4 to 22.6 μM,
whereas compounds 1−3 exhibited only weak cytotoxic activities on HT-29 cell. After HL-60 cells
were treated with the compounds, several apoptosis events like as chromatin condensation and the
increase of the population of sub-G1 hypodiploid cells were observed. These data supported that
the compounds might have potential for leukemia treatment.
Pdf see 090703bmcl-1
8. Isoplatensimycin: Synthesis and Biological Evaluation
In Press, Accepted Manuscript, Available online 27 June 2009
Ki Po Jang, Chan Hyuk Kim, Seong Wook Na, Hiyoung Kim, Heonjoong Kang, Eun Lee
Abstract: Isoplatensimycin, a novel analog of platensimycin, was synthesized via intramolecular
dipolar cycloaddition of a carbonyl ylide. Isoplatensimycin showed little activities against strains
of Staphylococcus aureus, but exhibited activities against some vancomycin-resistant enteroccoci.
Pdf see 090703bmcl-2
9. Ulmosides A and B: flavonoid 6-C-glycosides from Ulmus wallichiana, stimulating osteoblast
differentiation assessed by alkaline phosphatase
In Press, Accepted Manuscript, Available online 25 June 2009
Preeti Rawat, Manmeet Kumar, Kunal Sharan, Naibedya Chattopadhyay, Rakesh Maurya
Abstract: Three new compounds, ulmoside A (1) ulmoside B (3) and ulmoside C (8) along with
five known compounds were isolated from Ulmus wallichiana. Compounds 1-3 and 5 showed
promising osteogenic activity.
Pdf see 090703bmcl-3
10. Glycolipid ester-type heterodimers from Ipomoea tyrianthina and their pharmacological
activity
In Press, Accepted Manuscript, Available online 25 June 2009
Ismael León-Rivera, Gumersindo Mirón-López, Samuel Estrada-Soto, Francisco Aguirre-Crespo,
María del Carmen Gutiérrez, Gloria María Molina-Salinas, Gerardo Hurtado, Gabriel
Navarrete-Vázquez, Elizur Montiel
Abstract: Tyrianthins A (1) and B (2), two partially acylated glycolipid ester-type heterodimers
were isolated from a methanol-soluble extract of Ipomoea tyrianthina. Scammonic acid A was
determined as the glycosidic acid in both monomeric units. Tyrianthin A (1) (IC500.24 ± 0.09 μM
and Emax 81.80 ± 0.98%), and tyrianthin B (2) (IC50 0.14 ± 0.08 μM and Emax 87.68 ± 0.72%)
showed significant in vitro relaxant effect on aortic rat rings, in endothelium- and
concentration-dependent manners. Also, these compounds were able to increase the release of
GABA and glutamic acid in brain cortex, and displayed weak antimycobacterial activity.
Pdf see 090703bmcl-4
11. Synthesis, Characterization and Anti-Melanoma Activity of Tetra-O-substituted Analogs of
Nordihydroguaiaretic Acid
In Press, Accepted Manuscript, Available online 21 June 2009
Ross O. Meyers, Joshua D. Lambert, Nicole Hajicek, Alan Pourpak, John A. Kalaitzis, Robert T.
Dorr
Abstract:Novel derivatives of nordihydoguaiaretic acid were synthesized and tested for in vitro
and in vivo anticancer activity.
Pdf see 090703bmcl-5
12. Total Syntheses of a Conformationally Locked North-Type Methanocarba Puromycin
Analogue and a Dinucleotide Derivative (p NA)
Abstract: Natural products continue to serve as one of the best sources for discovery of
antibacterial agents as exemplified by the recent discoveries of platensimycin and platencin.
Chemical modifications as well as discovery of congeners are the main sources for gaining
knowledge of structure activity relationship of natural products. Screening for congeners in the
extracts of the fermentation broths of Streptomyces platensis led to the isolation of platencin A1, a
hydroxy congener of platencin. The hydroxylation of the tricyclic enone moiety negatively
affected the antibacterial activity and appears to be consistent with the hydrophobic binding
pocket of the FabF. Isolation, structure, enzyme-bound structure and activity of platencin A1 and
two other congeners have been described.
Pdf see 090703bmcl-6
Chem & Pharm Bull Vol. 57 (2009) , No. 7
13. Two New Acyclic Diterpene Glycosides from Fruits of Habanero, Capsicum chinense
Jong-Hyun Lee, Mona El-Aasr, Tsuyoshi Ikeda, Kana Oda, Hiroyuki Miyashita, Hitoshi
Yoshimitsu, Masafumi Okawa, Junei Kinjo and Toshihiro Nohara Release Date: 2009/07/01
Abstract:Four acyclic diterpene glycosides were extracted from Habanero, the fruits of Capsicum
chinense JACQ., which is known as one of the hottest peppers in existence. Two of these
glycosides were identified as capsianoside XIII and capsianoside XV. The other two were new
ones and were characterized as 3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl
17,19-dihydroxy-6E,10E,14Z-(3S)-geranyllinalool
17-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-[α-L-rhamnopyranosyl-(1→6)]-β-D-gluc
opyranoside
and
3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl
6E,10E,14Z-(3S)-17-hydroxy-geranyllinalool17-O-[3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopy
ranosyl
6′E,10′E,14′Z-(3′S)-13′R,19′-dihydroxy-geranyllinalool-16′-oyl
(16′→2)-[α-L-rhamnopyranosyl-(1→3)]-α-L-rhamnopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1
→6)]-β-D-glucopyranoside.
Pdf see 090703cpb-1
Chemistry - A European journal
14. A Straightforward Total Synthesis of (-)-Chaetominine (p NA)
Beatrice Malgesini, Barbara Forte, Daniela Borghi, Francesca Quartieri, Cesare Gennari, Gianluca
Papeo Published Online: Jun 27 2009 3:29AM DOI: 10.1002/chem.200900793
Abstract: A total synthesis of the tripeptide alkaloid (-)-chaetominine (1) was achieved in 9.3 %
overall yield starting from commercially available D-tryptophan methyl ester, based on a short and
straightforward (nine steps) sequence. The early stage introduction (first step) of the quinazolinone
moiety and the late stage introduction (penultimate step) of the hydroxy group allowed a synthetic
strategy devoid of protective groups. The key step of the process is the a-c tricyclic ring
construction via an unprecedented NCS-mediated N-acyl cyclization on an indole ring to give
tetrahydro-1H-pyrido[2,3-b]indole 11. In the penultimate step, oxidation of the tetracyclic
intermediate 14 with oxaziridine 15 gave only one of the four possible diastereoisomers, the
cis-diastereoisomer 16 resulting from the attack of the oxaziridine to the double bond face
opposite to the c-d ring substituents. In the last step, the complete stereocontrol of the Et3SiH/TFA
reduction of compound 16, probably involving a N-acyliminium ion, can be attributed to ring
constrain, which forces the b-c ring junction in the more stable cis-orientation. (-)-Chaetominine
(1) showed a negligible inhibitory activity on several cancer cell lines.
Pdf see 090703ceuj-1
15. Synthesis and Biophysical Studies on 35-Deoxy Amphotericin B Methyl Ester (p NA)
Alex M. Szpilman, Damiano M. Cereghetti, Jeffrey M. Manthorpe, Nicholas R. Wurtz, Erick M.
Carreira Published Online: Jun 19 2009 10:40AM DOI: 10.1002/chem.200900231
Abstract：The use of molecular editing in the elucidation of the mechanism of action of
amphotericin B is presented. A modular strategy for the synthesis of amphotericin B and its
designed analogues is developed, which relies on an efficient gram-scale synthesis of various
subunits of amphotericin B. A novel method for the coupling of the mycosamine to the aglycone
was identified. The implementation of the approach has enabled the preparation of 35-deoxy
amphotericin B methyl ester. Investigation of the antifungal activity and efflux-inducing ability
of this amphotericin B congener provided new clues to the role of the 35-hydroxy group and is
consistent with the involvement of double barrel ion channels in causing electrolyte efflux.
Pdf see 090703ceuj-2
Helvetica Chimica Acta (Volume 92 Issue 6 June 2009)
16. Chemical Constituents from Clerodendrum bungei and Their Cytotoxic Activities (p
1070-1079)
Shan-Shan Liu, Tong Zhou, Shu-Wei Zhang, Li-Jiang Xuan Published Online: Jun 23 2009
3:56PM DOI: 10.1002/hlca.200800392
Abstract: A new phenylethanoid glycoside, two new cyclohexylethanoids, one new phenolic
glycoside, and a new farnesane-type sesquiterpenoid, namely 2-phenylethyl 3-O-(6-deoxy-L-mannopyranosyl)clerodenone
A
-D-glucopyranoside (1), 6
(3),
-O-[(E)-caffeoyl] rengyoside B (2),
2-({6-O-[(4-hydroxy-3-methoxyphenyl)carbonyl]-
-D-glucopyranosyl}oxy)-2-methylbutanoic
acid
(4),
2-{(2S,5R)-5-[(1E)-4-hydroxy-4-methylhexa-1,5-dien-1-yl]-5-methyltetrahydrofuran-2-yl}propa
n-2-yl
-D-glucopyranoside (5), together with 16 known compounds, were isolated from the
roots of Clerodendrum bungei. All structures were elucidated by spectroscopic methods. The new
compounds showed modest in vitro inhibition of the proliferation of the HeLa human cervical
carcinoma cell line (CCL-2), with IC50 values in the range of 3.5-8.7 M, adriamycin being used
as positive control, with an IC50 value of 0.026±0.001 M.
pdf see 090703hca-1
J. Am Chem Soc asap
17. Total Synthesis of N-Acetylglucosamine-1,6-anhydro-N-acetylmuramylpentapeptide and
Evaluation of Its Turnover by AmpD from Escherichia coli
Dusan Hesek, Mijoon Lee, Weilie Zhang, Bruce C. Noll and Shahriar Mobashery
Publication Date (Web): July 1, 2009 (Addition/Correction) DOI: 10.1021/ja904230q
Abstract: The total syntheses of reported compound were accomplished in 15 linear steps.
Compound 1 is shown to be a substrate of the AmpD enzyme of the Gram-negative bacterium
Escherichia coli, an enzyme that removes the peptide from the disaccharide scaffold in the early
cytoplasmic phase of cell wall turnover.
Pdf see 090706jacs-1
18. Total Synthesis and Biological Evaluation of Cortistatins A and J and Analogues
Thereof
K. C. Nicolaou, Xiao-Shui Peng, Ya-Ping Sun, Damien Polet, Bin Zou, Chek Shik Lim and David
Y.-K. Chen
Publication Date (Web): July 1, 2009 (Article)
DOI: 10.1021/ja902939t
Abstract:Total syntheses of the highly selective antiproliferative natural products cortistatins A
(1) and J (5) in their naturally occurring enantiomeric forms are described. The modular and
convergent
strategy
employed
relies
on
an
intramolecular
oxa-Michael
addition/aldol/dehydration cascade reaction to cast the ABCD ring framework of the molecule
and both Sonogashira and Suzuki−Miyaura coupling reactions to assemble the necessary
building blocks into the required heptacyclic skeleton. A divergent approach from a late-stage
epoxy ketone leads to both target molecules in a stereoselective manner. The developed synthetic
technologies were applied to the construction of several analogues of the cortistatins which were
biologically evaluated and compared to the natural products with regards to their antiproliferative
activities against a variety of cancer cells. Analogues 8 and 81, lacking both the dimethylamino
and hydroxyl groups of cortistatin A, were found to exhibit comparable biological activity as the
parent compound, leading to the conclusion that such functionalities are not essential for
biological activity.
Pdf see 090706jacs-2
19. Total Synthesis of (−)-Himandrine
Mohammad Movassaghi, Meiliana Tjandra and Jun Qi Publication Date (Web): June 25, 2009
(Communication)
Abstract: We describe the first total synthesis of (−)-himandrine, a member of the class II
galbulimima alkaloids. Noteworthy features of this chemistry include a diastereoselective
Diels−Alder reaction in the rapid synthesis of the tricycle ABC-ring system in an enantiomerically
enriched form, the use of a formal [3+3] annulation strategy to secure the CDE-ring system with
complete diastereoselection, and successful implementation of our biogenetically inspired
oxidative spirocyclization of an advanced intermediate. The successful and direct late-stage
formation of the F-ring in the hexacyclic core of himandrine drew on the power of biogenetic
considerations and fully utilized the inherent chemistry of a plausible biosynthetic intermediate.
Pdf see 090706jacs-3
20. Identification, Characterization, and Bioconversion of a New Intermediate in
Valanimycin Biosynthesis
Ram P. Garg, Lawrence B. Alemany, Sean Moran and Ronald J. Parry
Publication Date (Web): June 23, 2009 (Communication) DOI: 10.1021/ja901243p
Abstract: The antibiotic valanimycin is a naturally occurring azoxy compound isolated from
Streptomyces viridifaciens. Detailed investigations have shown that valanimycin is derived from
l-valine and l-serine via the intermediacy of O-(l-seryl)isobutylhydroxylamine. Sequence
analysis of the valanimycin biosynthetic genes provides relatively few clues concerning the
nature of the later stages of the pathway. Two exceptions are provided by the vlmJ and vlmK
genes. The translation product of vlmJ exhibits similarity to diacylglycerol kinases, while the
translation product of vlmK exhibits a weak similarity to the MmgE/PrpD superfamily of
proteins. This superfamily includes 2-methylcitrate dehydratase. This communication describes
the isolation and structure elucidation of valanimycin hydrate from vlmJ and vlmK mutants of S.
viridifaciens. Additional studies have shown that the conversion of valanimycin hydrate into
valanimycin by S. viridifaciens requires both the vlmJ and vlmK genes and that VlmJ catalyzes
the ATP-dependent phosphorylation of the hydroxyl group of valanimycin hydrate prior to
VlmK-catalyzed dehydration.
Pdf see 090706jacs-4
J. Med. Chem
21. Discovery of the First Series of Small Molecule H5N1 Entry Inhibitors
Gaopeng Song, Sen Yang, Wei Zhang, Yingli Cao, Peng Wang, Ning Ding, Zaihong Zhang, Ying
Guo and Yingxia Li
Publication Date (Web): June 18, 2009 (Letter) DOI: 10.1021/jm900275m
Abstract: The occurrence of highly pathogenic avian influenza virus H5N1 highlights the urgent
need for new classes of antiviral drugs. Inhibition of H5N1 entry into cells may be an effective
strategy. We report the first three small molecule inhibitors saponins with 3-O-β-chacotriosyl
residue, which showed potent inhibitory activity with IC50 of 7.22-9.25 μM. The subsequent
SAR studies showed the 3-O-β-chacotriosyl residue was essential for the activity, and the
aglycone structure also affected the activity.
Pdf see 090706jmc-1
J. Nat. Prod. Chem
22. Characterization of a Dispiroketal Spirolide Subclass from Alexandrium ostenfeldii
Joy S. Roach, Patricia LeBlanc, Nancy I. Lewis, Rex Munday, Michael A. Quilliam and Shawna L.
MacKinnon
J. Nat. Prod., Articles ASAP (As Soon As Publishable) Publication Date (Web): July 2, 2009
(Article) DOI: 10.1021/np800795q
Abstract: A new subclass of spirolide marine toxins, represented by spirolides H (1) and I (2),
were isolated from the marine dinoflagellate Alexandrium ostenfeldii. Spirolides H and I are
structurally distinct from other spirolides in that they contain a 5:6 dispiroketal ring system rather
than the trispiroketal ring system characteristic of previously isolated spirolides. The structures
were assigned using a combination of spectrometric and spectroscopic techniques. Previously
isolated spirolides containing a cyclic imine moiety showed toxicity in the mouse bioassay.
Spirolide H contains this cyclic imine moiety but does not show toxicity in the mouse assay,
suggesting that the presence of the cyclic imine moiety is not the only structural requirement for
toxicity.
Pdf see 090706jnp-1
23. Antiproliferative Bistramides from Trididemnum cyclops from Madagascar
Brian T. Murphy, Shugeng Cao, Peggy Brodie, Jean Maharavo, Hanta Andriamanantoanina,
Pierre Ravelonandro and David G. I. Kingston J. Nat. Prod., Articles ASAP (As Soon As
Publishable) Publication Date (Web): June 25, 2009 (Note) DOI: 10.1021/np900072k
Abstract: Bioassay-guided fractionation of a marine extract from Trididemnum cyclops afforded
the new lipopeptide 39-oxobistramide K (1) and the known bistramides A (2) and D (3).
Structure elucidation of 1 was carried out by analysis of one- and two-dimensional NMR
spectroscopy and HRMS data. Bistramides have been reported to exhibit antiproliferative activity
in the nanomolar range against a number of tumor cell lines in vitro and in vivo. The isolate 1
was tested for antiproliferative activity against the A2780 cell line and exhibited an IC50 value
of 0.34 μM
Pdf see 090706jnp-2
24. Diterpenoids from the Mediterranean Brown Alga Dictyota sp. Evaluated as Antifouling
Substances against a Marine Bacterial Biofilm
Yannick Viano, Dominique Bonhomme, Mercedes Camps, Jean-Franois Briand, Annick
Ortalo-Magn, Yves Blache, Louis Piovetti and Grald Culioli
Publication Date (Web): June 23, 2009 (Article) DOI: 10.1021/np900102f
Abstract: Four new cyclized diterpenes, one xenicane (1) and three dolabellanes (2−4), were
isolated, along with seven previously reported metabolites [3β-hydroxydilophol (5), dictyols E (6)
and C (7), hydroxycrenulide (8), 9-acetoxy-15-hydroxy-1,6-dollabelladiene (9),
hydroxyacetyldictyolal (10), and fucoxanthin], from a Mediterranean species of Dictyota sp.
collected in Le Brusc Lagoon (French Mediterranean coast). Their structures, as well as their
relative configurations, were determined through extensive spectrometric (IR, HRESIMS, 1D
and 2D NMR) data analysis and molecular modeling studies and by comparison with those
reported in literature. Some of the isolated metabolites were evaluated for their antiadhesion
activity against a marine bacterial biofilm (Pseudoalteromonas sp. D41).
Pdf see 090706jnp-3
25. Discorhabdins Revisited: Cytotoxic Alkaloids from Southern Australian Marine
Sponges of the Genera Higginsia and Spongosorites
Mohamed El-Naggar and Robert. J. Capon
Publication Date (Web): June 19, 2009 (Addition/Correction) DOI: 10.1021/np9003596
Abstract:Chemical analysis of southern Australian marine sponges of the genera Higginsia and
Spongosorites has yielded examples of the discorhabdin class of alkaloids. These include the
known metabolites (+)-discorhabdin A (1), (+)-discorhabdin D (2), makaluvamine J (6), and
damirone A (7), together with four new analogues, (+)-dihydrodiscorhabdin A (3),
(+)-debromodiscorhabdin A (4), (+)-dihydrodiscorhabdin L (8), and (+)-discorhabdin X (5), with
the latter compound being the first reported example of a thio heterocycle flanked by
oxo-thio-acetal and azo-thio-acetal functionalities. Structures for the new compounds were
assigned on the basis of detailed spectroscopic interpretation.
Pdf see 090706jnp-4
26. Sipholane Triterpenoids: Chemistry, Reversal of ABCB1/P-Glycoprotein-Mediated
Multidrug Resistance, and Pharmacophore Modeling
Sandeep Jain, Ioana Abraham, Paulo Carvalho, Ye-Hong Kuang, Lamiaa A. Shaala, Diaa T. A.
Youssef, Mitchell A. Avery, Zhe-Sheng Chen and Khalid A. El Sayed
Publication Date (Web): June 17, 2009 (Article) DOI: 10.1021/np900091y
Abstract:This study reports the isolation of nine new terpenoids (2−10), possessing two novel
skeletons, from the Red Sea sponge Callyspongia (=Siphonochalina) siphonella. The identity of
these novel skeletons was based on X-ray crystallography and extensive spectral analyses. These
compounds were evaluated for their ability to reverse P-glycoprotein (P-gp)-mediated multidrug
resistance in human epidermoid cancer cells. Sipholenone E (3) was better than sipholenol A (1), a
known P-gp modulator from this sponge, in reversing the P-gp-mediated multidrug resistance.
Sipholenol L (6) and siphonellinol D (8) were nearly as active as sipholenol A. On the basis of
X-ray crystallographic data and the established identity of 3−7, the structure of sipholenol I (11) is
revised. A pharmacophore model of three hydrophobic points and two H-bond acceptors was
generated for the active sipholane P-gp modulators.
Pdf see 090706jnp-5
J Org Chem
27. Indoxamycins A−F. Cytotoxic Tricycklic Polypropionated from a Marine-Derived
Actinomycete
Seizo Sato, Fumie Iwata, Takako Mukai, Shoichi Yamada, Jiro Takeo, Akihisa Abe and Hiroyuki
Kawahara
Publication Date (Web): July 2, 2009 (Article) DOI: 10.1021/jo900667j
Abstract: Six antitumor antibiotics of a new structure class, indoxamycins A−F (1−6), were
isolated from a saline culture group of marine-derived actinomyces whose strains showed
approximately 96% sequence homology of 16S rDNA with the family streptomycetaceae. The
structures of these indoxamycins, which are unusual polyketides composed of six consecutive
chiral centers, were assigned by combined spectral and chemical methods. In feeding experiments
using a stable isotope label, indoxamycin A was assembled from propionate units initially forming
the “aglycon” pentamethyl indeno furan. The discovery of these unprecedented compounds from
marine-derived actinomycetes, a low gene homology genus, offers a significant opportunity for
drug discovery.
Pdf see 090706joc-1
28. Total Synthesis of Pteridic Acids A and B†
Dedicated to Prof. Vtor Francisco Ferreira (Universidade Federal Fluminenese - RJ) for his
outstanding contributions to the field of synthetic organic chemistry in Brazil.
Luiz C. Dias and Airton G. Salles, Jr.
Publication Date (Web): July 2, 2009 (Article) DOI: 10.1021/jo9010365
Abstract: The total synthesis of pteridic acids A and B is reported. The convergent asymmetric
synthesis involved the use of a diastereoselective ethyl ketone aldol reaction followed by an
efficient spiroketalization and provided pteridic acids A and B in 2.9% and 2.8% overall yield,
respectively.
Pdf see 090706joc-2
29. Progress toward the Total Synthesis of Psymberin/Irciniastatin A
Lauren E. Brown, Yakira R. Landaverry, James R. Davies, Kristin A. Milinkevich, Sandra Ast,
Joseph S. Carlson, Allen G. Oliver and Joseph P. Konopelski
Publication Date (Web): July 2, 2009 (Article) DOI: 10.1021/jo9009003
Abstract: In this paper, we describe our synthesis of four key building blocks for the total
synthesis of psymberin (1) and its C4 epimer (2). Despite early difficulties in processing material
to the advanced intermediate stage, we have been successful in developing high-yielding
syntheses for the pyran core, natural side chain, 4-epi side chain, and aryl fragments of the
molecule. Our findings from the optimization process are presented herein.
Pdf see 090706joc-3
30. Structural and Synthetic Investigations of Tanikolide Dimer, a SIRT2 Selective
Inhibitor, and Tanikolide seco-Acid from the Madagascar Marine Cyanobacterium
Lyngbya majuscula
Marcelino Gutirrez, Eric H. Andrianasolo, Won Kyo Shin, Douglas E. Goeger, Alexandre
Yokochi, Jrg Schemies, Manfred Jung, Dennis France, Susan Cornell-Kennon, Eun Lee and
William H. Gerwick Publication Date (Web): July 2, 2009 (Article) DOI: 10.1021/jo900578j
Abstract: Tanikolide seco-acid 2 and tanikolide dimer 3, the latter a novel and selective SIRT2
inhibitor, were isolated from the Madagascar marine cyanobacterium Lyngbya majuscula. The
structure of 2, isolated as the pure R enantiomer, was elucidated by X-ray experiment in
conjunction with NMR and optical rotation data, whereas the depside molecular structure of 3 was
initially thought to be a meso compound as established by NMR, MS, and chiral HPLC analyses.
Subsequent total synthesis of the three tanikolide dimer stereoisomers 4, 5, and ent-5, followed by
chiral GC−MS comparisons with the natural product, showed it to be exclusively the R,R-isomer
5. Tanikolide dimer 3 (= 5) inhibited SIRT2 with an IC50 = 176 nM in one assay format and 2.4
μM in another. Stereochemical determination of symmetrical dimers such as compound 3 pose
intriguing and subtle questions in structure elucidation and, as shown in the current work, are
perhaps best answered in conjunction with total synthesis.
Pdf see 090706joc-4
31. Benzothiazines in Synthesis. A Formal Total Synthesis of Pseudopteroxazole
Michael Harmata, Zhengxin Cai and Yugang Chen
Publication Date (Web): June 18, 2009 (Article) DOI: 10.1021/jo9009112
Abstract: A formal total synthesis of the antitubercular natural product was accomplished. This
work was undertaken to address certain stereochemical problems in our initial synthesis. By using
an ester group as a surrogate for a methyl group, we were able to intercept a key intermediate in
our first synthesis with better selectivity and greater convergence than had previously been the
case.
Pdf see 090706joc-5
Magn. Reson. Chem(Early view )
32. Complete 1H and 13C signal assignment of prenol-10 with 3D NMR spectroscopy (p n/a)
Maria Misiak, Wiktor Komiski, Maria Kwasiborska, Jacek Wójcik, Ewa Ciepichal, Ewa
Swiezewska Published Online: Jul 1 2009 5:50AM DOI: 10.1002/mrc.2473
Abstract: The complete assignment of 1H and 13C chemical shifts of natural abundance
prenol-10 is reported for the first time. It was achieved using 3D NMR experiments, which were
based on random sampling of the evolution time space followed by multidimensional Fourier
transform. This approach makes it possible to acquire 3D NMR spectra in a reasonable time and
preserves high resolution in indirectly detected dimensions. It is shown that the interpretation of
3D COSY-HMBC and 3D TOCSY-HSQC spectra is crucial in the structural analysis of prenol-10.
Pdf see 090707mrc-1
Organic Letters:
33. A Versatile Route to the Tulearin Class of Macrolactones: Synthesis of a Stereoisomer of
Tulearin A
Alexander L. Mandel, Vronique Bellosta, Dennis P. Curran and Janine Cossy
Publication Date (Web): June 25, 2009 (Letter) DOI: 10.1021/ol900936t
Abstract: A versatile synthetic approach to the tulearin class of macrolactones has been
developed and deployed to make a stereoisomer of tulearin A. The knowledge gained about
structure and synthesis will expedite the assignment of the stereostructure of this new anticancer
agent.
Pdf see 090707ol-1
34. Lobocrasol, a New Diterpenoid from from the Soft Coral Lobophytum crassum
Shih-Tseng Lin, Shang-Kwei Wang, Shi-Yie Cheng and Chang-Yih Duh
Publication Date (Web): June 24, 2009 (Letter) DOI: 10.1021/ol901070e
Abstract: Lobocrasol (1), possessing an unprecedented diterpenoid skeleton, was isolated from
the soft coral Lobophytum crassum. The structure of lobocrasol was established by extensive
analysis of spectroscopic data.
Pdf see 090707ol-2
35. Efficient Asymmetric Total Syntheses of Cryptocarya Triacetate, Cryptocaryolone, and
Cryptocaryolone Diacetate
Xiaolei Wang, Wenkuan Wang, Huaiji Zheng, Yingpeng Su, Tuo Jiang, Yongping He and
Xuegong She Publication Date (Web): June 19, 2009 (Letter) DOI: 10.1021/ol901024t
Abstract: Concise and efficient asymmetric total syntheses of three substituted α-pyrone-type
natural products have been accomplished via 7−9 steps from 5b in high overall yields, which
involve linchpin coupling, ring-closing metathesis, and a tandem sequence of deacetylation and
intramolecular oxa-Michael addition as the key steps.
Pdf see 090707ol-3
36. Plectosphaeroic Acids A, B, and C, Indoleamine 2,3-Dioxygenase Inhibitors Produced in
Culture by a Marine Isolate of the Fungus Plectosphaerella cucumerina
Gavin Carr, Wendy Tay, Helen Bottriell, Sarah K. Andersen, A. Grant Mauk and Raymond J.
Andersen Publication Date (Web): June 19, 2009 (Letter) DOI: 10.1021/ol900972j
Abstract: Laboratory cultures of the fungus Plectosphaerella cucumerina obtained from marine
sediments collected in Barkley Sound, British Columbia, yielded the novel alkaloids
plectosphaeroic acids A (1) to C (3). The alkaloids 1−3 are inhibitors of indoleamine
2,3-dioxygenase (IDO).
Pdf see 090707ol-4
37. Biomimetic Synthesis of Dimeric Metabolite Acremine G via a Highly Regioselective and
Stereoselective Diels−Alder Reaction
Elias Arkoudis, Ioannis N. Lykakis, Charis Gryparis and Manolis Stratakis
Publication Date (Web): June 18, 2009 (Letter) DOI: 10.1021/ol901004e
Abstract: The dimeric metabolite acremine G was synthesized featuring a highly regioselective
and stereoselective Diels−Alder reaction between a TBS-protected hydroquinone diene and a
structurally related alkenyl quinone. The major endo [4 + 2] adduct slowly transforms to acremine
G by the atmospheric air under the deprotection conditions (in situ generated HF).
Pdf see 090707ol-5
38. Structure and Formation of the Fluorescent Compound of Lignum nephriticum
A. Ulises Acua, Francisco Amat-Guerri, Purificacin Morcillo, Marta Liras and Benjamn Rodrguez
Publication Date (Web): June 17, 2009 (Letter) DOI: 10.1021/ol901022g
Abstract: The intense blue fluorescence of the infusion of Lignum nephriticum (Eysenhardtia
polystachya), first observed in the sixteenth century, is due to a novel four-ring
tetrahydromethanobenzofuro[2,3-d]oxacine which is not present in the plant but is the end product
of an unusual, very efficient iterative spontaneous oxidation of at least one of the tree’s
flavonoids.
Pdf see 090707ol-6
Tetrahedron
39. Chaetomugilins I–O, new potent cytotoxic metabolites from a marine fish-derived
Chaetomium species. Stereochemistry and biological activities
In Press, Accepted Manuscript, Available online 4 July 2009
Yasuhide Muroga, Takeshi Yamada, Atsushi Numata, Reiko Tanaka
Abstract: Chaetomugilins I–O were isolated from a strain of Chaetomium globosum originally
isolated from the marine fish Mugil cephalus, and their absolute stereostructures were elucidated
on the basis of spectroscopic analyses, including 1D and 2D NMR techniques and chemical
transformations. These compounds exhibited significant growth inhibition against cultured P388,
HL-60, L1210, and KB cell lines. In addition, chaetomugilin I showed selective cytotoxic activity
against 39 human cancer cell lines.
Pdf see 090707t-1
40. Mersiphyllines A and B from Kopsia. Determination of relative configuration at a
quaternary center via formation of an alkaloid-borane complex
In Press, Accepted Manuscript, Available online 24 June 2009
Yun-Yee Low, Subramaniam Gurusamy, Kuan-Hon Lim, Richard C.S. Wong, Ward T. Robinson,
Toh-Seok Kam
Abstract: Two new pentacyclic alkaloids, mersiphyllines A (1) and B (2), belonging to the novel
mersinine group, and incorporating carboxylic acid functionalities on a quaternary center, were
isolated from Kopsia singapurensis. The structures were determined by spectroscopic analysis.
Determination of the relative configuration at the quaternary center bearing the acid function was
facilitated by the formation of an alkaloid-borane complex. The structure of 1 was also confirmed
by X-ray diffraction analysis.
Pdf see 090707t-2
41. Total Synthesis of (–)-Incarvilline and (–)-Incarvillateine
In Press, Accepted Manuscript, Available online 24 June 2009
Fengying Zhang, Yanxing Jia
Abstract: An enantioselective, concise total synthesis of (–)-incarvilline and (–)-incarvillateine
has been achieved in longest linear 9 steps (24.3% overall yield) and in 11 steps (16.5% overall
yield) from (–)-carvone, respectively. The present synthesis features a notable Favorskii
rearrangement of the O-protected chlorohydrin derivative of (–)-carvone to construct four of the
five contiguous stereocenters on the bicyclic piperidine moiety and DMAP-catalyzed esterification
of incarvilline with α-truxillic acid anhydride to generate incarvillateine skeleton.
pdf see 090707t-3
42. A nature-inspired Diels–Alder reaction facilitates construction of the
bicyclo[2.2.2]octane core of andibenin B
In Press, Corrected Proof, Available online 21 June 2009
Jillian E. Spangler, Erik J. Sorensen
Abstract: A rapid synthesis of the bicyclo[2.2.2]octane core of andibenin B via a nature-inspired
intramolecular [4+2] cycloaddition is described. This cycloaddition permits the construction of a
sterically congested bicycle and simultaneously establishes three new all-carbon quaternary
stereogenic centers in a highly efficient fashion.
Pdf see 090707t-4
43. Excavatoids A–D, new polyoxygenated briaranes from the octocoral Briareum
excavatum
In Press, Corrected Proof, Available online 21 June 2009
Ping-Jyun Sung, Yin-Di Su, Gung-Ying Li, Michael Y. Chiang, Mei-Ru Lin, I-Chu Huang,
Jan-Jung Li, Lee-Shing Fang, Wei-Hsien Wang
Abstract: Three polyoxygenated briaranes, including two new compounds, excavatoids A (1) and
B (2), and a known metabolite, briaexcavatin I (3), were isolated from the cultured octocoral
Briareum excavatum. Moreover, the wild type B. excavatum, collected off southern Taiwan coast,
yielded two new 5,6-epoxybriaranes, excavatoids C (4) and D (5). The structures of new
compounds 1, 2, 4, and 5 were determined by spectroscopic methods and the structure of 1 was
further confirmed by X-ray diffraction data analysis. The X-ray structure for briaexcavatin I (3)
was also reported for the first time. Excavatoid A (1) is the first briarane which possesses six
hydroxy groups and a 17-methoxy group. Excavatoid C (4) is the first 12,13-secobriarane which
possesses a novel pentacyclic skeleton with an -lactone. Excavatoid D (5) displayed moderate
inhibitory effects on superoxide anion generation and elastase release by human neutrophils.
Pdf see 090707t-5
44. A radical mediated approach to the stereoselective formal total synthesis of (+)-Sch
642305
In Press, Corrected Proof, Available online 21 June 2009
Tushar Kanti Chakraborty, Rajarshi Samanta, Pulukuri Kiran Kumar
Abstract: A formal total synthesis of (+)-Sch-642305 is described. The synthesis, which
commenced from a simple chiral synthon (5S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one,
employed, as a key step, a radical mediated opening of a chiral epoxy alcohol intermediate with
Cp2Ti(III)Cl following an efficient method developed by us earlier. The resultant intermediate
radical was intramolecularly trapped by the electron deficient double bond present in the molecule
to give rise to its highly functionalized six-membered carbocyclic ring in stereoselective manner.
Pdf see 090707t-6
45. Eunicellin-Based Diterpenoids from the Cultured Soft Coral Klyxum simplex
In Press, Accepted Manuscript, Available online 18 June 2009
Bo-Wei Chen, Yang-Chang Wu, Michael Y. Chiang, Jui-Hsin Su, Wei-Hsien Wang, Tung-Yung
Fan, Jyh-Horng Sheu
Abstract: Eight new eunicellin-base diterpenoids, klysimplexins A–H (1–8), were isolated from a
cultured soft coral Klyxum simplex. Their structures were elucidated by spectroscopic methods,
particularly in 1D and 2D NMR experiments. The structure of 1 was further confirmed by a
single-crystal X-ray diffraction analysis and the application of modified Mosher's method.
Metabolites 2 and 8 were found to be cytotoxic toward a limited panel of cancer cell lines.
Pdf see 090707t-7
46. Enantioselective synthesis of phomallenic acid C by In- and Pd-mediated anti-SN2′
coupling
In Press, Corrected Proof, Available online 18 June 2009
Tomoko Kato, Ken Ishigami, Kazuaki Akasaka, Hidenori Watanabe
Abstract: Enantioselective synthesis of phomallenic acid C, an inhibitor of bacterial FAS II
pathway, was succeeded. Allenyldiyne structure was constructed by a direct anti-SN2′ coupling of
propargyl mesylate with diynylindium in the presence of palladium catalyst. Enantiomeric purity
was determined by Ohrui–Akasaka method to be 96% ee.
Pdf see 090707t-8
Tetrahedron Letters
47. Isolation, Enzyme-Bound Structure and Activity of Platensimycin A1 from
Streptomyces platensis
In Press, Accepted Manuscript, Available online 3 July 2009
Sheo B. Singh, Hiranthi Jayasuriya, Kithsiri B. Herath, Chaowei Zhang, John G. Ondeyka,
Deborah L. Zink, Sookhee Ha, Gopalakrishnan Parthasarathy, Joseph W. Becker, Jun Wang,
Stephen M. Soisson
Abstract: Inhibition of fatty acid synthesis is emerging as a valuable target for antibacterial agents.
Platensimycin and platencin are novel natural products that were reported recently to inhibit the
FabF and FabF/FabH condensing enzymes, respectively, present in the fatty acid biosynthetic
pathway. Selective inhibition of these enzymes by platensimycin and platencin accounts for their
potent antibiotic activity. We have continued our quest to find additional members of this class of
compounds leading to discovery of platensimycin A1, a hydroxylated congener. We report herein
the isolation, structure, antibacterial and enzymatic activity, and co-crystal structure bound to E.
coli FabF. The lower activity of platensimycin A1 suggests that substitution at C-14 is detrimental
for the activity.
Pdf see 090707tl-1
48. An efficient synthesis of oosporein
In Press, Corrected Proof, Available online 25 June 2009
Brian E. Love, Jeffrey Bonner-Stewart, Lori A. Forrest
Abstract: Fungal metabolite oosporein was prepared in four steps and 24% overall yield starting
from 2,5-dimethoxytoluene. It was demonstrated that treatment of phoenicin with pyrrolidine and
copper(II) acetate led to oosporein, whereas similar treatment of the isomeric ‘isophoenicin’
produced a benzofuran diquinone. No chromatography was required during any step of the
synthesis.
Pdf see 090707tl-2
49. Total synthesis of the natural isoprenylcysteine carboxyl methyltransferase inhibitor
spermatinamine
In Press, Corrected Proof, Available online 21 June 2009
José García, Raquel Pereira, Angel R. de Lera
Abstract: The first total synthesis of spermatinamine, an inhibitor of isoprenylcysteine carboxyl
methyltransferase (Icmt) with a bromotyrosine–spermine–bromotyrosine dimeric structure is
described.
Pdf see 090707tl-3
50. Expedient total syntheses of preclathridine A and clathridine A
In Press, Corrected Proof, Available online 21 June 2009
Panduka B. Koswatta, Carl J. Lovely
Abstract: A short and operationally simple total synthesis of the marine alkaloids preclathridine A
and clathridine A from a 4,5-diiodoimidazole derivative is described.
Pdf see 090707tl-4
51. Synthesis of indole alkaloid (−)-corynantheidol and formal synthesis of (−)-corynantheidine
via one-pot asymmetric azaelectrocyclization
Abstract:
The highly efficient asymmetric total synthesis of indole alkaloid, (-)-corynantheidol, containing a
2,4,5-trisubstituted piperidine core, was achieved using a new version of the one-pot
azaelectrocyclization reaction. The formal synthesis of (-)-corynantheidine was also achieved
using the common synthetic intermediate for these corynantheines.
Pdf see 090612tl-5
Part II Latest News/ Reviews
C & EN
1.June 17, 2009 Product SafetyRegulating TobaccoHistoric legislation gives FDA authority to
limit, remove harmful chemicals in products Britt E. Erickson
Detailed story see: http://pubs.acs.org/cen/news/87/i25/8725notw6.html
2. June 22, 2009 Volume 87, Number 25 p. 34
Synthetic Polymer Inspired By Nature Biomimetic polymer takes advantage of hydrogen
bonding to replicate the elasticity and toughness of the muscle protein titin Sophie L. Rovner
Detailed story see: http://pubs.acs.org/isubscribe/journals/cen/87/i25/html/8725scic3.html
3. June 1, 2009: Seeking Saltiness New findings on salty taste may inspire ways to trick the
tongue. For detailed story see: http://pubs.acs.org/cen/science/87/8722sci1.html
4. May 25, 2009: Alkenes Made Simple From Biomass Polyols Organic chemists have
devised a novel dideoxygenation method to convert polyhydroxyl compounds such as
glycerol into olefins.
For detailed story see: http://pubs.acs.org/isubscribe/journals/cen/87/i21/html/8721scic5.html
Reviews
Chem Review
1. Chemistry and Biology of Mycotoxins and Related Fungal Metabolites
Stefan Brse, Arantxa Encinas, Julia Keck and Carl F. Nising
Publication Date (Web): June 17, 2009 (Review) DOI: 10.1021/cr050001f
Abstract：A review with 1074 references giving a complete summary on the mycotoxins and
related fungal metabolites summarizing the isolation, structural determination, synthetic studies
and biological activities of the variolin, meridianin and meriolins.
Pdf see 090605cr-1
2. Marine Metabolites: The Sterols of Soft Coral
Nittala S. Sarma, Moturi S. Krishna, Sk. Gouse Pasha, Thota S. Prakasa Rao, Y. Venkateswarlu
and P. S. Parameswaran Publication Date (Web): May 12, 2009
(Review)DOI:10.1021/cr800503e
Abstract：A review with 280 references giving a complete summary on the marine metabolites
sterols from soft coral.
Pdf see 090605cr-2