Gerald A. Smith

Structural studies on the antibiotic vancomycin; the nature of the aromatic rings

It is shown that the antibiotic vancomycin contains five benzene rings. In a three-ring unit, connected through ether linkages, two sugars (glucose and vancosamine) are sequentially attached to a central pyrogallol system. A two-ring unit is connected as a biphenyl system, incorporating three phenolic OH groups. It is concluded that vancomycin contains carbamoyl and carboxy-groups. The identified units, plus the previously isolated aspartic acid and N-terminal N-methyl-elucine, appear to account for all, or almost all the carbon skeleton of vancomycin if reasonable assumptions are made regarding interconnection of the units through amide bonds.

Structural studies on the antibiotic vancomycin: evidence for the presence of modified phenylglycine and β-hydroxytyrosine units

Chemical and spectroscopic evidence is presented to support the presence of three oxygenated phenylglycine units in the molecule of the antibiotic vancomycin. The glycine (2 mol. equiv.) reported as a product of alkaline hydrolysis of vancomycin is believed to arise from the fission of two chloro-β-hydroxytyrosine units. The 1H n.m.r. spectrum of a crystalline degradation product, hexa-O-methyl-N-acetyl-CDPII, is in accord with the presence of the above units, as is the 13C n.m.r. spectrum (sp3 carbon atoms) of CDPII itself. The presence of two hydroxygroups in hexa-O-methyl-N-acetyl-CDPII is established through the preparation of a bisdinitrobenzoate.

Steroid analogues. Part 5. Synthesis of Δ9-6,7-dinor-5,8-seco-steroids viaΔ3-1,3,4-thiadiazolines

A general synthesis of symmetrical bi(cycloalkylidene)s is reported, involving successive reaction of an azine with hydrogen sulphide to give a 1,3,4-thiadiazolidine, oxidation to a Δ3-1,3,4-thiadiazoline, pyrolysis to a thiiran, and desulphurisation. The stereochemistry of the products and intermediates was elucidated by 1H n.m.r. spectroscopy with reference to the Woodward–Hoffmann rules and to conformation theory. The intermediate thiadiazolidines may also be prepared by direct condensation of a cycloalkanone with hydrazine and hydrogen sulphide, with different stereochemical consequences.A novel synthesis of mixed azines by oxidation of carboxyhydrazones with lead dioxide is described. Combined with the above process, this constitutes a general synthesis of unsymmetrical bicycloalkylidenes. This method has been used to prepare 3,17-disubstituted Δ9-6,7-dinor-5,8-secoestrenes. The stereochemistry at C-3 in these olefins and in the intermediate episulphides was assigned by correlation with known compounds, and the orientation of the sulphur atom in the episulphides was elucidated by 1H n.m.r. spectroscopy with reference to conformation theory and the Woodward–Hoffmann rules. Unexplained differences in the 1H n.m.r. spectra of secosteroidal epoxides and episulphides are described.

Gas-phase isomerizations in ion-radicals C4H8˙+ and C6H12˙+

Ions C4H8˙+ have been generated in the mass spectrometer by ionization of the butenes, methyl-cyclopropane, and cyclobutane, and by loss of H2O from ionized n-butanol, HF from ionized n-butyl fluoride, H2S from ionized n-butanethiol, and AcOH from ionized n-butyl acetate. Competing metastable transitions from the resulting C4H8˙+ ions indicate decomposition from common states in all cases. Similarly, metastable transitions from C6H12˙+ ions, generated from many different precursors, also indicate decomposition from common states.

Experiments towards a synthesis of antheridiol: a synthesis of biologic-ally active material

A conversion of diosgenin into a product exhibiting the biological activity of antheridiol (but at a lower level) is described. The product is either an active stereoisomer of antheridiol, or, more probably, a stereoisomer con-taminated with antheridiol. In the course of the synthesis novel conditions were used for (i) the reduction of a hindered ketone in the presence of ester and lactone functions and (ii) an oxidative demethoxycarbonylation reaction to introduce a double bond.

An efficient conversion of diosgenin into 22-oxocholesterol

Diosgenin has been converted in 50% overall yield into a 1 : 1 mixture of 20S- and 20R-22-oxocholesterols, from which the 20S-22-ketone (containing the natural stereochemistry at C-20) can be isolated in good yield via a repreated equilibration procedure.