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Stereoselective hydroxylation of the 0-lactam ester 8 is a key step in a total synthesis of AI-77-B 1.The AI-77s are a small family of 3,4-dihydroisocoumarin derivatives isolated from a culture broth of Bacillus pumilus AI-77.1 AI-77-B 1 exhibits biological activity against stress ulcers in rats, yet is non-central suppressive, non-anticholinergic and non-antihistaminergic.2 Aspects of the chemistry and synthesis of AI-77-B have been studied,3-5 the first total synthesis having been described in 1989.6 AI-77-B is a dipeptide derived from the 3,4-dihydroisocoumarin 2 and the amino acid 3. Since the latter is a 0-amino acid, it was decided to investigate its synthesis from a homochiral (3-lactam, introducing the hydroxy substituents by cis-hydroxylation. (3-Lactams have recently been used in other (3-amino acid syntheses.7 We now report a total synthesis of AI-77-B using this approach.The (3-lactam aldehyde 4 is available in five steps from aspartic acid,g'9 and was condensed with methyl bis(2,2,2- '3 trifluoroethy1)phosphonoacetare 510 to give the (Z)-a,p-unsaturated ester 7. Oxidation using a catalytic amount of osmium tetroxide and N-methylmorpholine-N-oxide was found to be moderately stereoselective, and gave a mixture of diols 9 and 11, ratio ca. 80 : 20. The major diol was shown to be 0 0 CO2H

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The synthesis and alkylation of [4.3.0]-bicyclic lactams, derived from 6-oxopipecolic acid, have been investigated. Alkylation can proceed with predominantly exo-diastereoselectivity, but the efficiency of this process depends on the substitution at the hemiaminal ether system. These products can be readily deprotected to give substituted hydroxymethyl lactams in good yield.