Joydeep Kant

Diastereoselective addition of Grignard reagents to azetidine-2,3-dione: Synthesis of novel Taxol® analogues

Abstract Synthesis and cytotoxicity properties of novel C-2′ analogues of paclitaxel are described. The analogues were synthesized using Holtons β-lactam approach to append the side chain on baccatin III. The key intermediate to the synthesis of novel analogues was prepared employing an unprecedented stereocontrolled addition of Grignard reagent to a chiral azetidine-2,3-dione.

A chemoselective approach to functionalize the C-10 position of 10-deacetylbaccatin III. Synthesis and biological properties of novel C-10 Taxol® analogues

Abstract A chemoselective approach to functionalize the C-10 position of 10-deacetyl baccatin III, a key intermediate for the semi-synthesis of paclitaxel, is described. The chemistry provides an easy access to a variety of C-10 hydroxyl derivatives, such as, ethers, esters, carbonates, carbamates, and sulfonates under mild conditions. The C-10 modified baccatin derivatives were further employed in the synthesis of novel biologically active Taxol® analogues.

Studies toward structure-activity relationships of taxol®: synthesis and cytotoxicity of taxol® analogues with C-2′ modified phenylisoserine side chains☆

Abstract Analogues of taxol with a modified phenylisoserine side chains were synthesized and evaluated as potential cytotoxic agents.

Enantioselective microbial reduction of 2-oxo-2-(1', 2', 3', 4'-tetrahydro-1', 1', 4', 4'-tetramethyl-6'-naphthalenyl)acetic acid and its ethyl ester

Abstract The chiral ester ethyl (2 R )-hydroxy-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′-naphthalenyl) acetate 2 and the corresponding acid 4 were prepared as intermediates in the synthesis of the retinoic acid receptor gamma-specific agonist ( R )-3-fluoro-4-[[hydroxy(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)acetyl]amino]benzoic acid 7 . Enantioselective reduction of ethyl 2-oxo-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′naphthalenyl)acetate 1 to alcohol 2 was carried out using Aureobasidium pullulans SC 13849 in 98% yield and with an enantiomeric excess (e.e.) of 96%. Among microorganisms screened for the reduction of 2-oxo-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′-naphthalenyl)acetic acid 3 to hydroxy acid 4 , Candida maltosa SC 16112 and two strains of Candida utilis (SC 13983, SC 13984) gave reaction yields of >53% with e.e.s of >96%.

Taxol® structure-activity relationships: synthesis and biological evaluation of taxol analogs modified at C-7

Abstract A series of taxol derivatives, modified at C-7, is described. This includes sulfonate, silylether, ester, carbonate, carbamate, fluoro, dehydro and deoxy derivatives. Biological evaluation shows that these modifications do not usually significantly compromise activity. However, none of the C-7 analogs prepared thus far have been shown to be better than taxol in both in vitro and in vivo assays.

A new strategy for the conversion of penams into cephems via allene chemistry

Abstract We describe an extension of the Morin rearrangement in which 3-norcephalosporins bearing sulfur substituents at C(3) are obtained directly from an allenic intermediate, which is efficiently prepared from penicillin V sulfoxide.

A stereocontrolled synthesis of cefprozil and related cephems via allenylazetidinones

Abstract A new method for the preparation of cephalosporins bearing carbon substituents of choice at C-3 is described. The approach involves 1,4-conjugate addition of an organocuprate to an allenylazetidinone to form a carbon-carbon bond followed by ring closure via intramolecular sulfenylation reaction.

Reaction of electron-deficient N-sulfinylanilines with chiral α-hydroxy acids: a new process for the synthesis of enantiomerically pure α-hydroxy amides

Abstract A practical procedure to prepare enantiomerically pure α-hydroxy amides from chiral α-hydroxy acids and electron-deficient anilines via N -sulfinylaniline derivatives has been developed.

Reactions of organocuprates with vinyl-triflates and related cephems: A novel approach to 3-substituted cephalosporins

Abstract Vinyl-triflates and related 3-substituted cephems readily undergo addition-elimination reactions with a variety of organocuprates to form new carbon-carbon bonds. This chemistry presents a novel approach to the synthesis of 3-alkyl, 3-aryl, and 3-alkenylcephalosporins.

Synthesis and antitumor properties of novel 14-β-hydroxytaxol and related analogues

Abstract Novel analogues of TAXOL ® with an additional hydroxyl group at the C-14 position were synthesized and evaluated as antitumor agents.