RESUMO
The direct, asymmetric α-amination of aldehydes has been accomplished via a combination of photoredox and organocatalysis. Photon-generated N-centered radicals undergo enantioselective α-addition to catalytically formed chiral enamines to directly produce stable α-amino aldehyde adducts bearing synthetically useful amine substitution patterns. Incorporation of a photolabile group on the amine precursor obviates the need to employ a photoredox catalyst in this transformation. Importantly, this photoinduced transformation allows direct and enantioselective access to α-amino aldehyde products that do not require postreaction manipulation.
Assuntos
Aldeídos/química , Aminas/química , Aldeídos/síntese química , Aminação , Aminas/síntese química , Catálise , Oxirredução , Fótons , EstereoisomerismoRESUMO
The importance for the right order of functional group introduction and manipulation (good timing) was demonstrated in the course of a total synthesis of phoslactomycin A. The synthetic strategy comprised a Cu(I)-thiophene carboxylate (CuTC, Liebeskind's reagent)-mediated coupling to introduce the Z,Z-diene at the final stage of the synthesis in the presence of a protected phosphate. Key features for the assembly of the C1-C13 fragment were an asymmetric dihydroxylation, an Evans-aldol reaction and an advanced protective group strategy. The C14-C21 fragment was accessible via an asymmetric 1,2-addition to cyclohexenone and a subsequent diastereoselective ketone reduction. One crucial task was the dihydroxylation of the C8-C9 alkene, the introduction of the C6-C7 double bond and the generation of the C25-nitrogen functionality. A second example consisted of the best sequence for the generation of the functional groups in the core part (first phosphorylation, second iodo-olefination, third azide/carbamate conversion). The synthetic solutions from this approach are compared with the already existing contributions in the phoslactomycin area.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Azidas/química , Produtos Biológicos/farmacologia , Compostos Organofosforados/síntese química , Alcenos/química , Antibacterianos/química , Antifúngicos/química , Antineoplásicos/química , Produtos Biológicos/química , Carbamatos/química , Catálise , Indicadores e Reagentes/química , Lactonas/síntese química , Lactonas/química , Lactonas/farmacologia , Estrutura Molecular , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Pironas , EstereoisomerismoRESUMO
A convergent total synthesis of the PP2A-inhibitor phoslactomycin A was achieved using a CuTC-mediated coupling of an alkenyl iodide C1-C13 fragment with an C14-C21 alkenyl stannane in the presence of a protected phosphate. Key features for the assembly of the C1-C13 fragment were an asymmetric dihydroxylation, an Evans-Aldol reaction, and a well-balanced protective group strategy. An asymmetric 1,4-addition to cyclohexenone was the key step in the preparation of the C14-C21 fragment.
Assuntos
Proteína Fosfatase 2/antagonistas & inibidores , Catálise , Lactonas/síntese química , Lactonas/química , Lactonas/farmacologia , Estrutura Molecular , Compostos Organofosforados/síntese química , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Pironas , Estereoisomerismo , Streptomyces/químicaRESUMO
A stereoselective synthesis of 7-dihydro-triocacarcinose B, a branched octose from the quinocyclines, has been achieved. The biocatalytic resolution of a Baylis-Hillman adduct and a subsequent ring-closing metathesis were used to assemble the molecular framework. Subsequent key steps were a highly stereoselective epoxidation and a regio- and stereoselective opening of the epoxide by allyl alcohol and HClO4 to introduce the C(3)-OH group in protected form. The 7-dihydro-triocacarcinose B could be converted into the corresponding 1,7-anhydrosugar.