Synthesis of (2R,5S)-dihydroxymethyl-(3R,4R)-dihydroxypyrrolidine (DGDP) via stereoselective amination using chlorosulfonyl isocyanate.
A stereoselective approach for synthesizing (2R,5S)-dihydroxymethyl-(3R,4R)-dihydroxypyrrolidine 1 (2,5-dideoxy-2,5-imino-d-glucitol, DGDP) was achieved using a seven-step approach starting from 2,3,4,6-tetra-O-benzyl-d-mannose (7). Key steps for the preparation of the title compound 1 involved the regioselective and diastereoselective amination of the cinnamyl anti-1,2-polybenzyl ethers 5 and 6 using chlorosulfonyl isocyanate (CSI) and ring cyclization to form the pyrrolidine ring. The reaction between anti-1,2-polybenzyl ether 5 and CSI in toluene at 0 degrees C afforded the corresponding anti-1,2-amino alcohol 4 as a major product with a diastereoselectivity of 16:1 in 76% yield. The mechanism underlying these reactions may be explained by the neighboring-group effect leading to the retention of stereochemistry.
Kim
In Su
IS
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Kim
Sin Jung
SJ
Lee
Jae Koo
JK
Li
Qing Ri
QR
Jung
Young Hoon
YH
D000470:Alkaloids / Q000138:chemical synthesis*; D000586:Amination; D029866:Derris / Q000737:chemistry; D050113:Imino Furanoses / Q000138:chemical synthesis; D017953:Isocyanates / Q000737:chemistry*; D008353:Mannitol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D011759:Pyrrolidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000470:Alkaloids; D050113:Imino Furanoses; D017953:Isocyanates; D011759:Pyrrolidines; C487390:chlorosulfonyl isocyanate; D008353:Mannitol; C043121:2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine