R. Wenger
Mar 14, 1984
Citations
0
Influential Citations
127
Citations
Quality indicators
Journal
Helvetica Chimica Acta
Abstract
The heptapeptide H-MeBmt-Abu-Sar-MeLeu-Val-MeLeu-Ala-OBzl (20) was synthesized for coupling with the previously described cyclosporine tetrapeptide sequence Boc-D-Ala-MeLeu-MeVal-OH (21). The product of the coupling, the undecapeptide Boc-D-Ala-MeLeu-MeLeu-MeVal-MeBmt-abu-Sar-MeLeu-Val-MeLeu-Ala-OBzl (22), was then deprotected and cyclized to cyclosporine (1). The tetrapeptide diastereoisomer Boc-D-ala-MeLeu-MeLeu-D-MeVAl-OH (23) could also be used as a starting material to produce selectively the desired undecapeptide 22. In this case, the N-methyl-D-valine unit, was selectively isomerized to the L-from by using the appropriate condensing agent. The diastereoisomeric undecapeptide Boc-D-ala-MeLeu-MeLeu-D-MeVal-MeBmt-Abu-Sar-MeLeu-Val-MeLeuAla-OBzl (24) was also synthesized starting from 21 by using the mixed pivalic anhydride method to selectively invert the configuration of the N-methyl-L-valine. The structure of the undecapeptide 24 was confirmed by deprotection and cyclization to ‘cyclosporin H’, a natural product known to have the structure [D-MeVal11]cyclosporine (2).