Synthesis of a Cyclic Depsipeptide via an Amide Cyclization
The synthesis of (S)-Pms-(R)-Pro-(S)-Ala-Aib-N(CH3)2 (12) has been achieved according to Scheme 3. For the formation of fragment 11, the reaction of Z-alanine (Z = benzyloxycarbonyl) and 3-dimethylamino-2,2-dimethyl-2H-azirine (1) has been used, whereby 1 serves as an aminoisobutyric-acid dimethylamide (Aib-N(CH3)2) equivalent. Treatment of a suspension of 12 in toluene with HC1 gas at 100° led to the cyclic depsipeptide 13 in 72% yield (Scheme 4). In presence of water, the acid 14 was isolated as the sole product. A mechanism for the formation of 13 and 14 via an oxazolinone intermediate, is postulated in Scheme 4.