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The readily availability of steroidal C(l7)-spirooxirans (VI), by the action of either dimethylsulphonium methylide or dimethyloxosulphonium methylide on 17-ketonesJg made the oxirans attractive as precursors of D-homoandrostane derivatives.l0 We envisaged either (a) the conversion of the oxiran into the amino-alcohol (HI), with subsequent use of nitrous acid as in the older route, or (b) the formation of a different 17,20-disubstituted compound (VII) suitable for a pinacolic or semipinacolic type of rearrangement. The requirement here was an effective ' leaving group ' (X) at C(20). We therefore studied the behaviour of the C(17)-spiro-oxirans with a variety of reagents providing nucleophilic species which might attack C(20).Pye$ayation of 3p-Hyd~oxy-~-homoandrost-5-en-l7a-one and -17-one.-The conversion of 3 p-hydroxyandrost-5-en-17-one into the C(17)-spiro-oxirans (VIa and b) followed essentially the published procedures>~~ though with minor modifications (see Experimental section). Incidentally we found that prolonged contact of the 3p-hydroxy-17-ketone with dimethylsulphonium methylide in the presence of an excess of trimethylsulphonium iodide gave the 3~-methoxy-compound in high yield. O-Methylation by this salt does not appear to have been reported previously, although trimethyloxosulphonium iodide is described as a methylating agent for phenols.11 This side reaction was avoided by limiting the reaction time to 1 h, after which the product no longer showed i.r. absorption at 1740 cm-l due to the 17-ketone.

Routes to putative N-acyl-D-ala-D-ala surrogates, beginning with the conversion of 4-, 5-, and 6-membered lactones into 5-, 6-, and 7-membered cyclic hydroxamates, are reported. The key step of the synthesis is trimethylaluminium-promoted cyclization of an ω-aminooxyester. The 7-membered cyclic hydroxamate crystallizes in a chair conformation. Extension of the reaction sequence to homoserine or homoserine lactone leads to cyclocanaline and N-acylated cyclocanalines. The 4-phenylacetamido derivative of cyclocanaline crystallizes in a boat conformation. The attachment of a 2-carboxypropyl substituent to the ring nitrogen of a 4-acylaminocyclocanaline has been effected, prior to cyclization, by coupling of the acyclic aminooxyester precursor to the triflate of benzyl lactate or, after cyclization, by coupling to tert-butyl α-bromopropionate in the presence of potassium fluoride – alumina, followed by removal of the protecting group in each case. A six-membered homolog of the antibiotic lactivicin has been synthesized by the reaction of 4-phenylacetamidocyclocanaline with benzyl 2-oxoglutarate in the presence of carbodiimide, followed by hydrogenolysis. Starting with methyl 2,4-dibromo-2,4-dideoxy-L-erythronate, which is available in two steps from L-ascorbic acid, these reaction sequences have been applied to the stereospecific synthesis of a D-alanine derivative whose nitrogen atom is enclosed within a 3,4-disubstituted [1,2]oxazinan-3-one. Key words: D-ala-D-ala surrogate, cyclocanaline, homolactivicin, peptidoglycan, trimethylaluminium.

The synthesis of a thymine derivative of (S)-2-hydroxy-4-(2-aminophenyl)butanoic acid, compound 1, was achieved in high enantiomeric purity. The acyclic pyrimidine analog (S)-1 is a useful building block for the synthesis of a novel class of oligomers, the aromatic peptide nucleic acids (APNA, Scheme ). The APNA tetramer 18 was prepared from the amino acid monomer (S)-1 using classical peptide synthesis. UV absorption spectra and 1H NMR data of this tetramer suggested that base stacking interactions in the APNA oligomers may be favorable.

~-Homo-5cr-androstan-17a-one, -1 i'-one, and -1 6-one, and the corresponding epimeric pairs of alcohols and acetates have been prepared. These are valuable reference compounds quasi-enantiomeric to derivatives monosubstituted in ring A. N.m.r. data are considered ; 0.r.d. and c.d. curves have been treated elsewhere.

The title compounds are amino acids whose nitrogen atom is enclosed in a six-membered cyclic hydroxamate bearing a C5-hydroxyl group. They belong to a proposed new family of antibacterial agents targeted to the penicillin receptor. The glycine and alanine members of the family have been synthesized, as racemates, in seven steps from the four-carbon synthon diketene and the tert-butyl esters of N-hydroxyglycine and N-hydroxyalanine. Numerous alternatives to diketene have also been examined, but these lead mainly to five-membered cyclic hydroxamates. The theoretical considerations that have led to this synthetic programme are discussed in some detail. They include analysis of the structures of natural and unnatural penicillin surrogates, analysis of the penicillin pharmacophore, and a treatment of the chemical reaction with which penicillin blocks bacterial cell wall synthesis. The glycine derivative exhibits marginal but real activity vs. Micrococcus luteus. The alanine derivative, which more closely resembles D-ala-D-ala, is fifty times more active. Two five-membered structural isomers of the glycine derivative are inactive. Key words: cyclocanaline, cycloserine, lactivicin, oxamazins, peptidoglycan, penicillin-binding proteins.

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[reaction: see text] The diastereoselective cyclization of bissulfonyl esters was investigated by varying both the size and the placement of the substituent on the tether adjoining the reacting centers. Substitution at either the alpha or beta position relative to the ester moiety gave diastereomeric ratios of (1-3):1, while gamma substitution dramatically increased the diastereomeric ratios to (6-20):1.