Braja G. Hazra

Synthesis and antimicrobial activity of β-lactam-bile acid conjugates linked via triazole

Synthesis of novel 1,2,3-triazole-linked beta-lactam-bile acid conjugates 17-24 using 1,3-dipolar cycloaddition reaction of azido beta-lactam and terminal alkyne of bile acids in the presence of Cu(I) catalyst (click chemistry) have been realized. These molecules were evaluated in vitro for their antifungal and antibacterial activities. Most of the compounds exhibited significant antifungal and moderate antibacterial activity against all the tested strains.

Steroidal Conjugates and Their Pharmacological Applications

Nature continues to be the main source of inspiration for synthetic chemists in their quest to make novel conjugates, which can have different physical, biological and medicinal properties. Nature makes these conjugates from mixed biosynthesis and some of these chimeras are found to exhibit unusual biological properties. During the past two decades design of such entities has been receiving increasing attention. Among the hybrid natural products, hybrids of steroid frameworks have attracted great attention due to the significant biological properties and numerous therapeutic effects of steroids. The developments made over the past few years in the isolation, design and synthesis of steroidal conjugates and their pharmacological applications are discussed in this review.

Synthesis and biological evaluation of bile acid dimers linked with 1,2,3-triazole and bis-β-lactam

We report herein the synthesis and biological evaluation of bile acid dimers linked through 1,2,3-triazole and bis-beta-lactam. The dimers were synthesized using 1,3-dipolar cycloaddition reaction of diazido bis-beta-lactams , and terminal alkynes derived from cholic acid/deoxycholic acid in the presence of Cu(i) catalyst (click chemistry). These novel molecules were evaluated in vitro for their antifungal and antibacterial activity. Most of the compounds exhibited significant antifungal as well as antibacterial activity against all the tested fungal and bacterial strains. Moreover, their in vitro cytotoxicities towards HEK-293 and MCF-7 cells were also established.

Stereoselective synthesis of (22R, 23R, 24S)-3β-hydroxy-5-ene-22, 23-dihydroxy-24-methyl-cholestane : a brassinolide intermediate from 16-dehydropregnenolone acetate

Abstract A new synthesis of the important aldehyde 1 from easily available 16-Dehydropregnenolone acetate (16-DPA) in high yield is described. The aldehyde 1 is converted to trio] 24, involving a stereoselective generation of all the four chiral centers in the brassinolide side chain. The important features of this synthesis is stereospecific generation of the acetate 14 through ene reaction using three different catalysts as well as regioselective wittig reaction on the acetoxy aldehyde 20. Conversion of triol 24 to brassinolide is known, hence this constitutes a formal total synthesis of brassinolide.

Stereoselective synthesis and antimicrobial activity of steroidal C-20 tertiary alcohols with thiazole/pyridine side chain

Stereoselective synthesis of novel steroidal C-20 tertiary alcohols with thiazole and pyridine side chain using Grignard reaction of steroidal ketones and thiazole/pyridine magnesium bromide have been realized. These molecules were evaluated in vitro for their antifungal and antibacterial activities. Most of the compounds exhibited significant antifungal and antibacterial activity against all the tested strains.

Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: impending synergistic agents

Tetrapeptides derived from glycine and beta-alanine were hooked at the C-3beta position of the modified cholic acid to realize novel linear tetrapeptide-linked cholic acid derivatives. All the synthesized compounds were tested against a wide variety of microorganisms (gram-negative bacteria, gram-positive bacteria and fungi) and their cytotoxicity was evaluated against human embryonic kidney (HEK293) and human mammary adenocarcinoma (MCF-7) cell lines. While relatively inactive by themselves, these compounds interact synergistically with antibiotics such as fluconazole and erythromycin to inhibit growth of fungi and bacteria, respectively, at 1-24 microg/mL. The synergistic effect shown by our novel compounds is due to their inherent amphiphilicity. The fractional inhibitory concentrations reported are comparable to those reported for Polymyxin B derivatives.

STEREOSELECTIVE SYNTHESIS OF A NEW HEXANOR(C23-C28)CASTASTERONE-20,22-ETHYL DIETHER FROM 16-DEHYDROPREGNENOLONE ACETATE AND ITS PLANT GROWTH PROMOTING ACTIVITY

Abstract Stereoselective synthesis of a new hexanor(C23–C28)castasterone-20,22-ethyl diether 22 has been achieved in sixteen steps from cheap and readily available 16-dehydropregnenolone acetate. This new brassinosteroid has shown typical brassin activity in mung bean epicotyl bioassay.

Resin catalysed ene reaction on 3β-toluene-p-sulfonoxy-(Z)-pregna-5,17(20)-diene : synthesis of (20S)-6β-methoxy-3α,5-cyclo-5α-pregnane-20-carboxyaldehyde+

Abstract Conversion of 17-keto steroid 2 in to 17(Z) ethylidene steroid 3 was achieved in high yields using a modified procedure. Ene reaction on 4 with paraformaldehyde in presence of acetic anhydride using various cation exchange resins as catalyst afforded stereospecifically the C-22 acetate 5 in excellent yields. For the first time cation exchange resins have been used as catalysts in ene reaction. Compound 5 was converted to C-22 aldehyde 1 using simple reaction sequence.

Synthesis of 11β-(4-dimethylaminophenyl)-17β-hydroxy-17α- (3-methyl-1-butynyl)-4, 9-estradien-3-one and 11β-(4-acetophenyl)- 17β-hydroxy-17α-(3-methyl-1-butynyl)-4, 9-estradien-3-one: two new analogs of mifepristone (RU-486)☆,☆☆,☆☆☆

From the structure activity relationship, two new analogs, 2 and 3, of the potent progesterone antagonist mifepristone 1 have been designed. The syntheses of these two analogs have been achieved in eleven steps through modified synthetic sequences and improved procedures starting from (+)-estrone. In comparison with mifepristone 1, the relative binding affinities of compound 2 for the progesterone receptor was found to be more, whereas that of compound 3 was less.

Cation exchange resin supported oxidation of alkylbenzenes and olefins using potassium permanganate

Rapid and efficient oxidation of alkylbenzene side chains at the benzylic positions as well as oxidative cleavage of olefins with potassium permanganate in presence of solid polymeric cation exchange resins in good yields is reported.