David F. Crowe

Synthesis and testing of 17aβ-hydroxy-7α-methyl-d-homoestra-4, 16-dien-3-one: a highly potent orally active androgen

Abstract The title compound, 17aβ-hydroxy-7α-methyl- d -homoestra-4, 16-dien-3-one (3), was synthesized in five steps (17% overall yield) from 7α-methylestrone methyl ether (5) and was found to possess oral androgenic activity, in excess of other known androgens, without using 17α-alkyl substitution. (Steroids 55 :59–64, 1990)

Synthesis of pentacyclic lα,11-(2-oxethano) steroids

Abstract Treatment of a 1α,2α-methyleneandrostan analog (4) with hydrobromic acid/acetic acid gives an apparent intramolecular homoconjugate ring-opening, which serves as the key step in the synthesis of a new type of pentacyclic steroid analogs (2).

Generation and reaction of 2,4-dienolate ions from Δ4-3-keto-steroids with lithium hexamethyldisilazane

Reaction of Δ4-3-keto-steroids with lithium hexamethyldisilazane yields 2,4-dienolate ions which can be methylated at C-2 or trapped as 2,4-dienolsilyl ethers.

Semisynthetic aminoglycoside antibacterials. Part II. Synthesis of gentamicin X2 and related compounds

Gentamicin X2, naturally occurring aminoglycoside antibiotic produced as a minor component together with the clinically important gentamicin C complex by Micromonospora purpurea, has been synthesized by glycosylation of suitably protected garamine derivatives. The synthesis of the α-glycoside was accomplished by means of the Lemieux–Nagabhushan reaction as well as by using a Koenigs–Knorr reaction. The latter reaction was also used to prepare 4-O-β-analogue of gentamicin X2. The syntheses of other analogues of gentamicin X2, namely 4-O-[2-amino-2-deoxy-α-D-mannopyranosyl], 4-O-[2-amino-2-deoxy-α-D-galactopyranosyl], 4-O-[2-amino-2-deoxy-α- and -β-D-glucofuranosyl], 4′-O-[2-amino-2-deoxy-α-D-glucopyranosyl], 4-O-α-D-glucopyranosyl, 4-O-α-D-talopyranosyl, and 4-O-2-deoxy-α-D-galactopyranosyl derivatives of garamine, are also described.

Semisynthetic aminoglycoside antibacterials. Part V. Synthesis of pentosyl and related derivatives of garamine

The application of the Koenigs–Knorr and Lemieux–Nagabhushan reactions to the synthesis of a variety of novel 4-O-pentofuranosyl and 4-O-pentopyranosyl derivatives of garamine is described. The solution conformations of these novel pentosyl aminocyclitols have been assigned on the basis of 13C n.m.r. data.

Semisynthetic aminoglycoside antibacterials. Part I. Preparation of selectively protected garamine derivatives

N-Alkoxycarbonyl and N-acyl derivatives of sisomicin, an unsaturated aminoglycoside antibiotic, have been demonstrated to undergo ready acid-catalysed hydrolysis to the novel pseudodisaccharide garamine [O-(3-deoxy-4-C-methyl-3-methylamino-β-L-arabinopyranosyl)-(1 → 6)-2-deoxy-D-streptamine]. Alternative procedures and routes for the selective protection of various hydroxy-groups in the garamine molecule are discussed. The selectively protected garamine derivatives constitute useful intermediates for the preparation of a wide variety of novel semisynthetic aminoglycoside antibacterials related to the clinically important gentamicins.

A novel 11-enolate ion of a pregna-1,4-diene-3,11-dione from sodium bistrimethylsilylamide

Reaction of a steroidal 11-ketone with sodium bistrimethylsilylamide in tetrahydrofuran solution generates the 9(11)-enolate anion.