Structure reassignment and synthesis of Jenamidines A1/A2, synthesis of (+)-NP25302, and formal synthesis of SB-311009 analogues.
The proposed structures of jenamidines A, B, and C (1-3) were revised to jenamidines A1/A2, B1/B2, and C (8-10). Jenamidines A1/A2 (8) were synthesized from activated proline derivative 43 by conversion to 26 in two steps and 50% overall yield. Acylation of 26 with acid chloride 38d gave 39d, which was deprotected with TFA and then mild base to give 8 in 45% yield from 26. (-)-trans-2,5-Dimethylproline ethyl ester (49) was prepared by the enantioselective Michael reaction of ethyl 2-nitropropionate (51) and methyl vinyl ketone (50) using modified dihydroquinine 60 as the catalyst. Further elaboration converted 49 to natural (+)-NP25302 (12). A Wittig reaction of proline NCA (76) with ylide 79 gave 72 as a 9/1 E/Z mixture in 27% yield, completing a one-step formal synthesis of SB-311009 analogues.
Duvall
Jeremy R
JR
Department of Chemistry, MS 015, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Wu
Fanghui
F
Snider
Barry B
BB
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011392:Proline / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry
D019086:Bridged Bicyclo Compounds, Heterocyclic; C478487:NP 25302; D011725:Pyridines; D011744:Pyrimidinones; D011763:Pyrrolizidine Alkaloids; C414143:SB 311009; C479696:jenamidine A; D011392:Proline