Premium
A Gram‐Scale Batch and Flow Total Synthesis of Perhydrohistrionicotoxin
Author(s) -
Brasholz Malte,
Macdonald James M.,
Saubern Simon,
Ryan John H.,
Holmes Andrew B.
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201001435
Subject(s) - gram , scale (ratio) , n gram , flow (mathematics) , computer science , mechanics , geography , geology , physics , natural language processing , cartography , bacteria , paleontology , language model
The total synthesis of the spiropiperidine alkaloid (−)‐perhydrohistrionicotoxin (perhydro‐HTX) 2 has been accomplished on a gram scale by employing both conventional batch chemistry as well as microreactor techniques. ( S )‐(−)‐6‐Pentyltetrahydro‐pyran‐2‐one 8 underwent nucleophilic ring opening to afford the alcohol 10 , which was elaborated to the nitrone 13 . Protection of the nitrone as the 1,3‐adduct of styrene and side‐chain extension to the unsaturated nitrile afforded a precursor 17 , which underwent dipolar cycloreversion and 1,3‐dipolar cycloaddition to give the core spirocyclic precursor 18 that was converted into perhydro‐HTX 2 . The principal steps to the spirocycle 18 have successfully been transferred into flow mode by using different types of microreactors and in a telescoped fashion, allowing for a more rapid access to the histrionicotoxins and their analogues by continuous processing.