Total synthesis and correct absolute configuration of malyngamide U.
The enantioselective synthesis of the previously proposed structure of malyngamide U (1) was accomplished in 18 steps from (S)-(+)-carvone. The key steps involved a hydroxymethylation of (S)-(+)-carvone and an asymmetric Henry reaction of aldehyde (+)-5, as well as condensation with the acid 3. The 1H and 13C NMR data of the synthetic compound 1 were not consistent with the data of the reported malyngamide U. The C-2' epimer of compound 1 was therefore synthesized by a similar reaction sequence. While the NMR data of C-2' epimer 23 were in full agreement with those of the reported product, the discrepancy in the specific rotation data suggested the correct structure of malyngamide U should be structure 2, in which the absolute configuration of the amine part was enantiomeric with that in compound 23. Then the correct absolute configuration of revised malyngamide U (2) was confirmed by the similar synthesis from (R)-(-)-carvone.
Li
Yang
Y
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, People's Republic of China.
Feng
Jian-Peng
JP
Wang
Wen-Hua
WH
Chen
Jie
J
Cao
Xiao-Ping
XP
D000438:Alcohols / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D003512:Cyclohexanones / Q000138:chemical synthesis* / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
D000438:Alcohols; D000447:Aldehydes; D003512:Cyclohexanones; D005229:Fatty Acids, Monounsaturated; C474704:malyngamide U