John D. Elliott

Asymmetric synthesis via acetal templates. 15. The preparation of enantiomerically pure mevinolin analogs

Abstract An efficient asymmetric synthesis of the hydroxylactone moiety of mevinolin 1 is described. The key step is the TiCl 4 -catalyzed coupling reaction of acetals 3a and 3b derived from (R)-1,3-butanediol with 1,3-bis(trimethylsilyloxy)-1-methoxybuta-1,3-diene 4 to give the δ-alkoxy-β-keto ester 5 .

Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A synthase by antibiotic 1233A and other β-lactones

3-Hydroxy-3-methylglutaryl CoA synthase was shown to be inhibited in a time-dependent, irreversible manner by compounds containing the substituted beta-lactone functionality found in the natural product 1233A. The rate of inactivation (kinact) was found to approach the rate of catalysis (kcat). The inactivation was irreversible over several hours. A related compound lacking the hydroxymethyl substituent on the beta-lactone ring is a reversible inhibitor and is competitive with respect to acetylCoA. The results are consistent with beta-lactone ring opening by the active site Cys to form an enzyme bound thioester.

The photochemical rearrangement of a steroidal dienol triflate

Abstract Photolysis of the steroidal dienol triflate 3 in pyridine solution using a medium pressure mercury lamp leads to the formation of 6β-trifluoromethyl enone 5 in 78% yield. The structure of compound 5 was confirmed by x-ray analysis.

The synthesis of novel bridged A ring steroids

Abstract The novel bridged A ring steroid 1 was synthesized as a potential inhibitor of steroid 5α-reductase. The structure of the key synthetic intermediate, pentacyclic enedione 2 was confirmed by x-ray analysis.

The preparation of 9-alkylthiofluorenes from biphenyl-2-carboxaldehydes

Abstract Upon treatment with ethanethiol and boron trifluoride etherate, the biphenyl-2-carboxaldehyde 1 has been found to undergo facile cyclization to the 9-ethylthiofluorenes 2 .