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Janine Cossy

Publications and source records attributed to Janine Cossy.

At least 19 recordsLinked to original sources
PubMed2007

Total synthesis of herbimycin A.

[structure: see text] Hsp90 has recently emerged as a promising biological target for treatment of cancer. Herbimycin A and other members of the benzoquinoid ansamycin class of natural products are known to inhibit Hsp90 activity. The total synthesis of herbimycin A was achieved from the commercially available Roche ester 1 by using allylmetals to control the stereogenic centers at C6, C7, C10, C11, and C12 and a ring-closing metathesis to control the (Z)-double bond of the (E,Z)-dienic moiety.

Benzoquinones↗
PubMed2006

Free-radical approaches to stemoamide and analogues.

Two approaches allowing access to the tricyclic stemona backbone are presented. Both approaches rely on a free-radical cyclization reaction as the key step. In the formal synthesis of (+/-)-stemoamide, the construction of the A ring of the natural product was achieved via a 5-exo-trig radical cyclization with atom transfer. The two diastereoisomers issuing from this cyclization showed different reactivity while forming the seven-membered ring of the final product. In the second part of this study, a 7-exo-trig free radical cyclization was realized allowing access to the (+/-)-9,10-bis-epi-stemoamide. This reaction was highly stereoselective and allowed the control of three of the four contiguous stereocenters present in the molecule.

Cyclization↗
PubMed2006

Ring expansion of functionalized octahydroindoles to enantiopure cis-decahydroquinolines.

A new synthetic entry to enantiopure cis-decahydroquinolines is reported. Endo and exo derivatives of cis-1-benzyl-2-(hydroxymethyl)octahydroindol-6-one ethylene acetal undergo ring enlargement upon treatment with TFAA and then Et3N (thermodynamic conditions) to give enantiopure 1-benzyl-3-hydroxydecahydroquinolin-7-one derivatives in 77 and 82% yield, respectively. For 2-(1-hydroxyethyl) analogues, the best synthetic result is obtained from the (2S,1'R) endo isomer, which under kinetic reaction conditions (MsCl, THF, -20 degrees C, then AgOAc at rt ) gives the expanded product in 54% yield.

Hydrogen↗
PubMed2006

Total synthesis of (-)-spongidepsin.

[structure: see text] A convergent and rapid stereoselective synthesis of (-)-spongidepsin has been achieved from the Roche ester in 14 steps with an overall yield of 13%.

Animals↗
PubMed2006

Biological evaluation of newly synthesized quinoline-5,8-quinones as Cdc25B inhibitors.

Cdc25B protein phosphatase represents an attractive potential therapeutic target for small molecule intervention because of its central role in positively regulating cyclin dependent kinases and thus cell proliferation, as well as its elevated levels observed in many human tumors. Among the most potent previously identified Cdc25 inhibitors have been quinoline quinones, which have a rich legacy as therapeutic agents but have also been associated with nonspecific interactions. In this study, we have interrogated the structure-activity relationship of a focused series of C2-, C3-, or C4-modified quinoline-5,8-quinones on Cdc25B inhibition in vitro. Substitution at the C3-position in this small chemical series were slightly superior to substitutions at the C3-position. For all compounds, recombinant human Cdc25B was approximately 5-fold more sensitive compared to recombinant human PTP1B. Two compounds inhibited HeLa cell growth with IC50 values of approximately 2 microM. Consistent with other para-quinones, some members of this series generated intracellular reactive oxygen species and the in vitro enzyme inhibition was mitigated by addition of reductants or catalase. These results indicate that chemical modifications on the pyridine core are tolerated, providing additional sites for future structural modification of this biologically active pharmacophore.

Cell Cycle Proteins↗
PubMed2006

Rearrangement of homoallylic alcohols induced by DAST.

[reaction: see text] Treatment of beta,gamma-unsaturated monoprotected 1,2-diols with diethylaminosulfur trifluoride (DAST) allows the stereoselective formation of beta,gamma-unsaturated aldehydes in good yields and with a good transfer of chirality.

Journal Article↗
PubMed2005

Synthetic approaches and total synthesis of natural zoapatanol.

[structure: see text] The total synthesis of (+)-zoapatanol utilizing an intramolecular Horner-Wadsworth-Emmons olefination and an enantioselective Sharpless dihydroxylation as the key steps has been achieved. An advanced oxepene intermediate has been obtained by applying a ring-closing metathesis to an unsaturated enol ether.

Molecular Conformation↗
PubMed2005

Total synthesis of (+/-)-mycothiazole and formal enantioselective approach.

[Reaction: see text] A total synthesis of (+/-)-mycothiazole and a formal enantioselective approach have been achieved from 2,4-dibromothiazole. A chain extension of a homoallylic alcohol proceeding through an unsaturated sultone intermediate, generated by ring-closing metathesis, was used as a key step for the elaboration of the conjugated (Z)-dienol moiety.

Antineoplastic Agents↗
PubMed2005

Selective methodologies for the synthesis of biologically active piperidinic compounds.

The synthesis of optically active substituted piperidines has been achieved by using four different methodologies. The first one is an intramolecular nucleophilic displacement of activated alcohol moieties that was used to build up the piperidine ring of (-)-prosophylline and (-)-slaframine, and the second one is a ring-closing metathesis of unsaturated amines which was employed in the synthesis of (+)-sedamine and 4a,5-dihydrostreptazoline. The third methodology is the alpha-functionalization of N-Boc piperidines which was particularly useful in the synthesis of argatroban, and the fourth one is a ring expansion of prolinols to 3-chloropiperidines or 3-hydroxypiperidines which was utilized to synthesize (-)-paroxetine, (-)-pseudoconhydrine, the piperidine ring of (-)-velbanamine and (+)-zamifenacin.

Alkaloids↗