Enantioselective construction of a polyhydroxylated pyrrolidine skeleton from 3-vinylaziridine-2-carboxylates: synthesis of (+)-DMDP and a potential common intermediate for (+)-hyacinthacine A1 and (+)-1-epi-australine.
We report an enantioselective synthesis of the polyhydroxylated pyrrolidine alkaloid (+)-DMDP. The key steps in the synthesis were guanidinium ylide mediated asymmetric aziridination, stereospecific ring opening of trans-3-vinylaziridine-2-carboxylate with an oxygen nucleophile, iodine-mediated 5-endo-trig amino cyclization, and Prévost displacement. In addition, a potential common intermediate for the polyhydroxylated pyrrolizidine alkaloids (+)-hyacinthacine A(1) and (+)-1-epi-australine was synthesized from a diastereoisomeric cis-aziridine coformed in the asymmetric aziridination using the same strategy. A rationale for the diastereoselectivity observed for the iodine-mediated amino cyclization reactions is proposed on the basis of the heats of formation of the products.
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo, Chiba 260-8675, Japan.
Yukari
Y
Kondo
Noriyuki
N
Suzuki
Masato
M
Takahashi
Takuya
T
Kumamoto
Hyuma
H
Masu
Tsutomu
T
Ishikawa
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D000470:Alkaloids; D002264:Carboxylic Acids; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; D014753:Vinyl Compounds; C508850:hyacinthacine A1; C059794:australine; C032519:pyrrolidine