Synthetic studies on the DEF-rings of FR182877 and hexacyclinic acid

A synthesis of model DEF-rings of the polyketide anti tumor natural products FR182877 and hexacyclinic acid has been achieved. The key steps in the synthesis are an intramolecular Pd(0) catalyzed allylic substitution reaction, which was used to generate a 9-membered carbocycle, and a novel transannular iodocyclization reaction which furnished the DF-rings of both natural products.     

A new simple route to deoxyamino sugars from non-sugar material: synthesis of d-tolyposamine and 4-epi-d-tolyposamine and formal synthesis of d-vicenisamine

A new, simple strategy has been formulated for the synthesis of deoxyamino sugars from a non-sugar starting material. Starting from the enantiomerically pure diol obtained from ethyl sorbate by Sharpless asymmetric dihydroxylation, the synthesis of two types of 2,3,4,6-tetradeoxy-4-amino sugars—d-tolyposamine and 4-epi-d-tolyposamine—, and formal synthesis of 2,4,6-trideoxy-4-amino sugar—d-vicenisamine—were performed.     

Cyclisation reactions of bis-protected guanidines

The cyclisation of N-allyl- and N-homoallylguanidines using DMDO or I₂/K₂CO₂ leading to novel heterocycles is reported.     

Regio- and stereochemical aspects in the synthesis of homoallylic alcohols from benzoins and their iodocyclisation to 2,3-diphenyltetrahydrofurans

Indium mediated allylation, crotylation and cinnamylation of benzoins and its substituted derivatives in THF-H₂O (2/1) provide a range of homoallylic alcohols. In general, the benzoins undergo allylation and crotylation in a sluggish manner compared to those observed earlier in the case of α-hydroxy aldehydes and are significantly affected by the electronic features of both the benzoin and indium organometallic reagent. The reactions exhibit higher order of diastereoselectivities than those observed for α-hydroxy aldehydes. The cinnamylation though proceeds in a highly diastereoselective manner but is restricted to only benzoin and 4,4′-dichlorobenzoin. The homoallylic alcohols undergo I₂ mediated intramolecular diastereoselective cyclization to provide 2,3-diphenyltetrahydrofuran derivatives. The relative stereochemistries in tetrahydrofurans and homoallylic alcohols have been assigned by coupling constants, NOE experiments and in one case by X-ray crystallography.     

Rapid synthesis of 1-deoxygalactonojirimycin using a carbamate annulation

A remarkably efficient synthesis of the biologically important iminosugar 1-deoxygalactonojirimycin (DGJ) is presented. Key to this strategy is the development of a novel carbamate annulation reaction that favours formation of a six-membered carbamate-containing piperidine skeleton over its five-membered counterpart.     

Iodocyclisation and rearrangement reactions of mono-protected allyl substituted guanidines

The iodocyclisation of a range N-allyl and N-homoallylguanidines using I₂/K₂CO₃ has been found to lead to a series of novel heterocycles which undergo selective rearrangements on variation of the reaction conditions, and predictable protecting group migration in the presence of trifluoroacetic acid in methanol.     

Iodocyclisations reactions of Boc- and Cbz-protected N-allylguanidines

The cyclisation of mono-protected and bis-protected guanidines 8a–j under standard iodocyclisation conditions (I₂/K₂CO₃) gave the guanidine heterocycles 9–25 via either a direct cyclisation or by a cyclisation/ring-contraction process, which could be controlled by careful selection of conditions.     

A simple, two-step synthesis of 3-iodoindoles

2-Halo-anilines, protected as the corresponding sulfonamides or carbamates, can be converted very efficiently into 3-iodoindoles by sequential Sonogashira coupling with a 1-alkyne and 5-endo-dig iodocyclisation. Azaindoles can also be obtained using this methodology.     

De-novo approach for a unique spiro skeleton-1,7-dioxa-2,6-dioxospiro[4.4]nonanes

2-Oxoglutaric acid (1) underwent facile indium mediated allylation with allyl bromide (2), and ethyl 4-bromocrotonate (3), cinnamyl bromide (4) and subsequent in situ dehydration to provide respective 5-oxotetrahydrofuran-2-carboxylic acids 5-7 (90-95%). The reaction of 1 with 3 and 4 proceeded with high regio and stereo selectivity to provide only γ-addition products with syn stereochemistry as ascertained from their cyclic products. Compounds 5-7 underwent diastereoselective iodocyclization to provide respective 1,7-dioxa-2,6-dioxospiro[4.4]nonanes 8-13. The relative stereochemistries have been ascertained by single crystal X-ray structures, NOE experiments and coupling constants in ¹H NMR spectra.