ABSTRACT
A highly efficient one-pot multistep process involving an asymmetric Pd(II)-catalyzed Overman rearrangement and a Ru(II)-catalyzed ring-closing metathesis reaction has been developed for the preparation of (R)- or (S)-aminocyclopenta-2-enes. The rapid strategy employed and the relatively mild conditions of the one-pot process allowed the multigram synthesis of the carbocycles in high enantiomeric excess (92% ee). The synthetic utility of these compounds was demonstrated by the stereoselective incorporation of hydroxyl groups, generating cis-4- and cis-5-aminocyclopenta-2-en-1-ols, important building blocks for medicinal chemistry.
Subject(s)
Cyclopentanes/chemical synthesis , Chemistry, Pharmaceutical , Cyclopentanes/chemistry , Molecular Structure , Palladium/chemistry , Ruthenium/chemistry , StereoisomerismABSTRACT
Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM ether-directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor D-erythro-sphinganine and the antitumor agent (+)-spisulosine, whereas the Overman rearrangement of chiral allylic trichloroacetimidates generated by the asymmetric reduction of an α,ß-unsaturated methyl ketone allowed rapid access both to D-ribo-phytosphingosine and L-arabino-phytosphingosine.
Subject(s)
Lipids/chemical synthesis , Sphingosine/analogs & derivatives , Sphingosine/chemical synthesis , Lipids/chemistry , Molecular Conformation , Sphingosine/chemistryABSTRACT
The first total synthesis of clavaminol A and C, (2R,3S)-2-amino-3-alkanols from the Mediterranean ascidian Clavelina phlegraea has been achieved in 29% overall yield. The key step involved a palladium(II)-catalysed directed Overman rearrangement to create the C-N bond and install the erythro configuration while a one-pot, tributyltin hydride-mediated reduction allowed simultaneous formation of the methyl side-chain and N-acetyl group. Similarly, the first total synthesis of clavaminol H was completed in 48% overall yield using an approach that also provided the cytotoxic des-acetyl analogue.
Subject(s)
Ceramides/chemical synthesis , Molecular Structure , Oxidation-ReductionABSTRACT
A new approach for the stereoselective synthesis of the bicyclic guanidine alkaloid (+)-monanchorin has been developed using a palladium(ii)-catalysed MOM-ether directed Overman rearrangement to establish the second stereogenic centre and a cross metathesis reaction to generate the carbon backbone. In the final stage, a one-pot acid mediated deprotection of aldehyde, guanidine and hydroxyl groups gave an intermediate that underwent facile cyclisation to (+)-monanchorin.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Guanidines/chemical synthesis , Porifera/chemistry , Alkaloids/chemical synthesis , Alkaloids/chemistry , Animals , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Guanidines/chemistry , Molecular Structure , StereoisomerismABSTRACT
A stereoselective synthesis of (+)-physoperuvine, a tropane alkaloid from Physalis peruviana Linne has been developed using a one-pot tandem aza-Claisen rearrangement and ring closing metathesis reaction to form the key amino-substituted cycloheptene ring.
