Brevetoxin b HO K H Meo Me、Ho H Me HoMe、Ho G H A B C D 0 M K C. Nicolaou. 1995
Brevetoxin B K. C. Nicolaou, 1995 O O O O O O O O O O O H O O Me H H H H H H Me H H H HO H Me H H Me Me H H H Me Me A B C D E F G H I J K
EF HH Brevetoxin B is a marine neurotoxin most commonly associated with red tides Annually responsible for the deaths of thousands of marine organisms The structure of this poison was identified in 1981 by Lin, Nakanishi, and Clardy The framework consists of a single carbon chain folded into eleven fused rings Twenty three stereocenters are present in the molecule
Introduction • Brevetoxin B is a marine neurotoxin most commonly associated with Red Tides – Annually responsible for the deaths of thousands of marine organisms • The structure of this poison was identified in 1981 by Lin, Nakanishi, and Clardy. • The framework consists of a single carbon chain folded into eleven fused rings. • Twenty three stereocenters are present in the molecule O O O O O O O O O O O H O O Me H H H H H H Me H H H HO H Me H H Me Me H H H Me Me A B C D E F G H I J K
Third generation Retrosynthetic approach TBSO 1: brevetoxin B 85 EFG
Third Generation Retrosynthetic Approach O O O O O O O O O O O O O Me H H H H H H Me H H H HO H Me H H Me Me H H H Me Me A B C D E F G H I J K 1: brevetoxin B O O O O O O O O O O OTPS Me H H H H H H Me H H H TBSO H Me H H Me Me EtS H Me Me A B C D E F G I J K EtS HO 85 O O O O O O O Me H H H H H H Me H Me H H Me Me Me A OTMS PPh3 O O O H H OTBS EtS H Me I EtS H H O J K OTPS + 87 86 B C D E F G
Retrosynthetic Approach Cont OTBS ☆一8 Me OTMS E FG PPh3 C TBSo、:CHo . OH OHOHOH 99: D-mannitol 79: D-mannose
Retrosynthetic Approach Cont. O O O O O O O Me H H H H H H Me H Me H H Me Me Me A OTMS PPh3 87 B C D E F G OH OH OH OH OH OH TBSO CHO Me PivO + 99: D-mannitol 97 O O O H H OTBS EtS H Me I EtS H H O J K OTPS 86 HO O OH OH HO OH 79: D-mannose
Total Synthesis Construction of Key Intermediates 86 and 87 Meo me Me OTMS H。MeH E FG AB C OTBS 87 EtS EtS OTPS H 86
Total Synthesis Construction of Key Intermediates 86 and 87 O O O O O O O Me H H H H H H Me H Me H H Me Me Me A OTMS PPh3 87 B C D E F G O O O H H OTBS EtS H Me I EtS H H O J K OTPS 86