Studies on the synthesis of (2S,3R)-3-hydroxy-3-methylproline via C2-N bond formation.
A new efficient synthesis of (2S,3R)-3-hydroxy-3-methylproline (3) is reported. During the course of a recent study on the Lewis acid promoted intramolecular opening of an epoxide by a carbamate NH, a highly concerted rearrangement was unexpectedly observed. Further investigations of substrate generality show that delta-carbamate-alpha,beta-epoxide esters commonly underwent similar rearrangements with the aid of Lewis acids. Retrosynthetic analysis of such a C(2)-N disconnection can lead to an efficient synthesis of (2S,3R)-3-hydroxy-3-methylproline (3) in high enantio purity. Stereochemistries were established by a Sharpless asymmetric dihydroxylation and a diastereoselective reductive amination.
Shen
Jun-Wei
JW
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Qin
Dong-Guang
DG
Zhang
Hong-Wang
HW
Yao
Zhu-Jun
ZJ
D000586:Amination; D000970:Antineoplastic Agents / Q000737:chemistry; D006900:Hydroxylation; D010456:Peptides, Cyclic / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013237:Stereoisomerism
C449928:(2,3)-3-hydroxy-3-methylproline; D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C121868:polyoxypeptin A; D011392:Proline