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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.