ABSTRACT
The total synthesis of the marine alkaloid halichlorine is described, based on an approach that involves constructing the fully substituted asymmetric center at an early stage. The five-membered ring is formed by 5-exo-trig radical cyclization and the unsaturated six-membered ring by a process that formally represents a sequential combination of conjugate addition and S(N)2' displacement-a method that is general for making bicyclic compounds with nitrogen at a ring fusion position. A formal synthesis of (+)-halichlorine is also reported, based on the development of a general method for preparing optically pure piperidines. The key step of this method, which was used to make one of our intermediates, is the Claisen rearrangement of a 4-vinyloxy-3,4-dihydro-2H-pyridine-1-carboxylic acid benzyl ester. Such O-vinyl compounds are easily generated in situ from the corresponding alcohols, which are themselves readily assembled from serine and terminal acetylenes.
Subject(s)
Alkaloids/chemical synthesis , Piperidines/chemistry , Spiro Compounds/chemical synthesis , Alkaloids/chemistry , Cyclization , Molecular Conformation , Piperidines/chemical synthesis , Spiro Compounds/chemistry , StereoisomerismABSTRACT
The intramolecular aminomercuration of gamma-alkenylamines 1a, 1b and 4 was shown to afford the 5-endo-trig cyclized product exclusively in good yield. The utility of pyrrolidine derivatives thus obtained from D-glucose derived gamma-alkenylamines 1a and 1b was demonstrated in the synthesis of 1-deoxycastanospermine (3a) and 1-deoxy-8a-epi- castanospermine (3b).
Subject(s)
Alkaloids/chemical synthesis , Amines/chemistry , Glucose/chemistry , Indolizines/chemical synthesis , Mercury/chemistry , Alkaloids/chemistry , Cyclization , Indolizines/chemistryABSTRACT
This paper describes an efficient route for the synthesis of known and novel griseolic acid analogues 1d and 1e, respectively. The key intermediate dioxabicyclo derivative 6, with the required stereochemical orientation at C6, was obtained by rhodium acetate catalyzed reaction of d-glucose derived alpha-diazo-beta-keto ester 5 in a novel high-yielding methodology.
