The primary hydroxyl group of [D-serine](8)-cyclosporin (1b) was alkyl
ated with isopropyl bromoacetate to provide the O-alkylated compound I
c. Then the secondary hydroxyl group was acetylated to give Id. The al
lylic methyl group of the MeBmt was brominated giving le. Bromide le w
as converted to the azide If. Transesterification of the isopropyl est
er If to the methyl ester Ig and subsequent hydrolysis provided acid I
h. Reduction of the azide gave the amino acid ii. The bromide of le wa
s also replaced by an acetate to give 1j which was hydrolyzed to give
the hydroxy acid Ik. The amino acid ii and the hydroxy acid Ik both we
re cyclized to the bridged cyclosporin lactam 2a and lactone 2b, respe
ctively. Degradation of the MeBmt residue of the acid 1l with ozone fo
llowed by reduction gave the hydroxy acid 3 which was cyclized to a mi
xture of the bridged lactone 4 and the dimeric bislactone 5.