Dinanath F. Rane

Total synthesis and absolute stereochemistry of the antifungal dipeptide Sch 37137 and its 2S,3S - isomer

Abstract The absolute stereochemistry of the epoxide moiety in Sch 37137 has been established as 2R, 3R by its synthesis from L-tartaric acid. .

A novel synthesis of cis-1-[[6-chloro-3-[(2-chloro-3-thienyl)methoxy]-2,3-dihydrobenzo[b]thien-2-yl]methyl]1h-imidazole: A new class of azole antifungal agents

Abstract Ring contraction of cis -3-bromo-7-chloro-3,4-dihydro-2H-1-benzothiopyran-4-ol 4 in the presence of imidazole results in formation of cis -6-chloro-2,3-dihydro-2-(1H-imidazol-1-ylmethyl) benzo[b]thiophene-3-ol 8 as the major product. The structure of 8 was defined unequivocally by X-ray analysis of a solvated (ethyl acetate) and an unsolvated crystal form. Alkylation of 8 with 3-(bromomethyl)-2-chlorothiophene gave cis -1-[[6-chloro-3-[(2-chloro-3-thienyl)methoxy]-2,3-dihydrobenzor[b] thien-2-yl]methyl]lH-imidazole 9 , a representative of a new class of azole antifungal agents.

Aqueous Diels-Alder reactions of electron deficient 2-arylfurans: a highly stereoselective route to 2,2,5-trisubstituted tetrahydrofurans towards a novel class of orally active azole antifungals

Aqueous Diels-Alder reactions 1 of halogenated 2-arylfurans with acetylenedicarboxylates made available previously inaccessible adducts (2, 2a, 7, and 8) which were successfully elaborated in a general stereocontrolled route to the title compounds

TOTAL SYNTHESIS OF THE ANTIFUNGAL CYCLIC DEPSIPEPTIDES SCH 57697 AND AUREOBASIDIN A

Abstract A novel cyclic depsinonapeptide antifungal 1a (Sch 57697) and its isomer 1b were synthesized by a fragment coupling approach and this methodology was applied to the total synthesis of the natural product aureobasidin A. Synthetic strategies for coupling of N-methyl amino acids with minimal racemization are discussed. Biological evaluation of isomers 1a and 1b demonstrated the importance of chirality at the β-hydroxy-N-methylvaline (OHMeVal) position.

Synthesis of substituted 1H-imidazol-1-ylmethylpiperidines. Facile separation of 1,4- and 1,5-disubstituted imidazoles

The synthesis of several 1H-imidazol-1-ylmethylpiperidines is described. A method for the regioselective isolation of 1,4-disubstituted imidazoles utilizing the selective quaternization of the 1,5-disubstituted regioisomer was developed.

Overview Anti-infectives: Recent advances in anti-HIV agents

Human immunodeficiency virus or HIV, is generally agreed to be the causative agent of Acquired Immunodeficiency Syndrome (AIDS). The chemotherapy and chemoprevention of AIDS continues to present challenges to biologists and chemists in both academic and pharmaceutical research. HIV is a lentivirus, a member of the retrovirus family and in addition to the typical retrovirus env, gag, and pol genes, HIV also contains the complex regulatory genes tat, m, neJ and the additional auxiliary genes viJ vpr, and vpu. HIV enters cells by the binding of its envelope glycoprotein gp 120 to the CD4 receptors of Human T4 lymphocytes which are normally involved in the defence against invading organisms. w can also spread to adjacent cells by syncytia formation: fusion of an infected cell with one that is not infected. Most certainly HIV uses other mechanisms to enter uninfected cells. Once inside the cell, the virus uses its own enzyme, an RNA dependent DNA polymerase (reverse transcriptase), to make a DNA copy of its genome which can then insert itself into the genome of the host cell. From this point, a combination of host and viral enzymes is used to make new virus particles which can burst from the cell, resulting in cell death and spreading infection.

Semisynthetic aminoglycoside antibacterials. Part 11. Solution conformations of semisynthetic and naturally occurring aminoglycoside antibiotics

A critical analysis of the 13C n.m.r. spectral data for a wide range of naturally occurring aminoglycoside antibiotics, as well as for a diverse assortment of semisynthetic aminoglycoside antibacterials, has revealed new insights into the solution conformation of these clinically important drugs. Correlation of the Δδc values for C-4 and C-6 determined in going from deoxystreptamine to the pseudo di-or tri-saccharides, as well as changes in the chemical shifts of C-1′ and C-1″, has revealed that these molecules adopt a wide range of well defined conformations in solution, that are dependent not only on the structure, but also the pH. The limitations of the ‘Nagabhushan–Daniels Rule,’ which has been reported to break down when applied to some classes of aminoglycosides, are discussed in the light of these new observations.

The synthesis of 2,2,24- trisubstituted oxetanes as new azole antifungal agents

Abstract Synthesis and biological activities of cis - and trans - 2,2,4 - trisubstituted oxetanes 4 and 5 are described. The key diol intermediates 9 and 10 exhibited exceptionally good in vitro and in vivo antifungal activity.