ABSTRACT
A highly diastereoselective indium-mediated allylation of 2-N-acetyl glycosyl sulfinylimines in brine under mild reaction conditions is reported. The method allows the achievement of a highly remarkable dichotomous selectivity for substrates, providing a single diastereoisomer of the product in 80-98% yield. With chiral (S)-homoallylic sulfinamide (RS)-5 and (RS)-8 formed as key intermediates, two potent anti-influenza agents, zanamivir and zanaphosphor, were synthesized in 50% and 41% overall yields, respectively.
Subject(s)
Indium , Salts , Antiviral Agents/pharmacologyABSTRACT
The potent anti-influenza agents, zanamivir and its phosphonate congener, are synthesized by using a nitro group as the latent amino group at C4 for asymmetric aza-Henry reaction with a chiral sulfinylimine, which is derived from inexpensive d-glucono-δ-lactone to establish the essential nitrogen-containing substituent at C5. This method provides an efficient way to construct the densely substituted dihydropyran core of zanamivir and zanaphosphor without using the hazardous azide reagent.
Subject(s)
Antiviral Agents/pharmacology , Aza Compounds/pharmacology , Influenza, Human/drug therapy , Orthomyxoviridae/drug effects , Zanamivir/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Aza Compounds/chemical synthesis , Aza Compounds/chemistry , Humans , Microbial Sensitivity Tests , Molecular Conformation , Zanamivir/chemical synthesis , Zanamivir/chemistryABSTRACT
Simple and mild methods for the synthesis of allenes, employing indium- and zinc-mediated dehalogenation reactions of vicinal dihalides in an aqueous solvent, are described. By using these procedures, various allenylmethyl aryl ethers and monosubstituted allenes have been prepared in good to excellent yields.
Subject(s)
Alkadienes/chemical synthesis , Antineoplastic Agents/chemical synthesis , Chemistry, Pharmaceutical/methods , Ethers/chemical synthesis , Green Chemistry Technology , Halogens/chemistry , Alkadienes/pharmacology , Antineoplastic Agents/pharmacology , Catalysis , Ethers/pharmacology , Humans , Indium/chemistry , Molecular Structure , Neoplasms/drug therapy , Solutions , Stereoisomerism , Water , Zinc/chemistryABSTRACT
Under tin-mediated Barbier-type reaction conditions, hydration of enol ethers takes place to form aldehydes that undergo allylation reactions. By using this process, various homoallylic alcohols and 2-halohomoallylic alcohols are produced in good to excellent yields.
