Structures of minor components of the validamycin complex.
complicated oligosaccharides using NMRspectroscopy have developed quite remarkably. The structure of validamycin G (VM-G),43 the most recently discovered congener was established by making use of these techniques. Wehave now used NMRto reinvestigated the position of the glycosidic linkage of the minor components which had remained obscure. The results were first disclosed in a patent application,53 though without experimental data. Here we discussed the structures of the minor components with experimental results. To elucidate the unidentified positions of the glucosidic linkage by *H NMRspectroscopy, VM-B~ F were acetylated with acetic anhydride and pyridine to give the corresponding peracetyl derivatives. The chemical shifts of 1-H and l'-H of the peracetates, recognized in the region of 3.2~3.6 ppm, indicate that the imino group is not acetylated. Therefore, these peracetates must be dodeca-O-acetyl validamycin B (Ac-
Stereoselective synthesis of (+)-valienamine starting from the naturally abundant (−)-shikimic acid
Abstract A stereoselective synthesis of the pharmaceutically useful pseudo-aminosugar (+)-valienamine 1 is described. Epoxide 2 was first prepared via four steps in 79.7% overall yield starting from the naturally abundant (−)-shikimic acid. Epoxide 2 was then converted into the vicinal dihydroxyl compound 3 in 96% yield via a highly regio- and stereoselective water-mediated epoxide opening. Compound 3 was transformed into compound 4 in 86% yield over two steps via ester-reduction and benzylation of the three hydroxyl groups. Compound 4 was converted into azido compound 5 in 90% yield via an S N 2-type nucleophilic substitution of the OMs leaving group with sodium azide. Ruthenium-catalyzed stereoselective dihydroxylation of compound 5 afforded dihydroxyl compound 6 in 91% yield. Compound 6 was transformed into compound 7 in 92% yield via selective mono-acetylation of the less-hindered hydroxyl group. Dehydration of tertiary alcohol 7 via an acid-mediated elimination furnished olefinic compound 8 in 85% yield. Finally, compound 8 was converted into the title compound 1 in 91% yield over two steps via deprotection and Lindlar-catalyst-promoted highly selective hydrogenation of the azido group (N 3 ) in the presence of a double bond. (+)-Valienamine 1 was thus synthesized starting from the naturally abundant (−)-shikimic acid via 13 steps in 38.3% total yield.
Inhibitors of monoamine oxidase. Influence of methyl substitution on the inhibitory activity of beta-carbolines.
A number of tetrahydro and aromatic β -carbolines, mostly with a methyl substituent at various positions, were synthesized and their in vitro inhibitory activities on monoamine oxidase evaluated. Substitution of a methyl group at the N-9 nitrogen of tetrahydro- β -carboline gave a potent competitive inhibitor of the enzyme. Methyl groups at C-1 of both tetrahydro and aromatic β -carbolines generally reduced the potency, whereas introduction of a methyl group at the N-2 nitrogen of tetrahydro- β -carboline gave a compound of equal activity.