Total synthesis

About: Total synthesis is a research topic. Over the lifetime, 25578 publications have been published within this topic receiving 489319 citations.

Total synthesis of (+)-fendleridine (aspidoalbidine) and (+)-1-acetylaspidoalbidine.

Abstract: A total synthesis of the Aspidosperma alkaloids (+)-fendleridine and (+)-1-acetylaspidoalbidine is detailed, providing access to both enantiomers of the natural products and establishing their absolute configuration. Central to the synthetic approach is a powerful intramolecular [4+2]/[3+2] cycloaddition cascade of a 1,3,4-oxadiazole in which the pentacyclic skeleton and all the stereochemistry of the natural products are assembled in a reaction that forms three rings, four C−C bonds, and five stereogenic centers including three contiguous quaternary centers, and introduces the correct oxidation state at C19 in a single synthetic operation. The final tetrahydrofuran bridge is subsequently installed in one step, enlisting an intramolecular alcohol addition to an iminium ion generated by nitrogen-assisted opening of the cycloadduct oxido bridge, with a modification that permits release of useful functionality (a ketone) at the cleavage termini.

A versatile and efficient synthesis of carbinolamine-containing pyrrolo[1,4]benzodiazepines via the cyclization of N-(2-aminobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetals: total synthesis of prothracarcin

Abstract: A versatile and efficient synthesis of carbinolamine-containing pyrrolo[1,4]benzodiazepines (or the corresponding imine forms) of types 2, 7, and 8 is described that involves mercuric chloride mediated cyclization of the corresponding N-(2-aminobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetals. This new synthesis has significant advantages over previously existing methods in that (a) catalytic hydrogenation is not involved in the cyclization process, thus allowing preservation of unsaturation in the product, (b) all steps are mild and take place in high yields, (c) the success of the reaction is apparently independent of substituent effects, (d) the reaction proceeds with retention of stereochemistry at the aldehyde-bearing carbon, and (e) it can be readily adapted for the convergent synthesis of a variety of analogues. In addition to the synthesis of some model carbinolamine-containing compounds, the overall utility of this procedure is demonstrated by the total synthesis of prothracarcin (2d), a natural product with antitumor activity from Streptomyces umbrosus. This allowed confirmation of the E configuration previously assigned to the C2-ethylidene side chain of prothracarcin.

Total Synthesis of Macrolactin A with Versatile Catalytic, Enantioselective Dienolate Aldol Addition Reactions.

Abstract: A highly convergent total synthesis of macrolactin A (1) utilizes modern asymmetric catalytic C–C coupling methods. The longest linear sequence in the route is 16 steps with an average yield of 86% per step. This total synthesis is valuable, because 1, which has been shown to possess activity against HIV, is not readily accessible from its natural source, a taxonomically unclassified deep-sea bacterium.

The Total Synthesis of (±)-Ginkgolide B

Abstract: The total synthesis of the potent PAF antagonist ginkgolide B has been accomplished. The complex architecture of ginkgolide B which includes six rings, eleven stereogenic centers, ten oxygenated carbons, and four contiguous fully substituted carbons is a daunting challenge for chemical synthesis. The synthesis of ginkgolide B was accomplished through a stereoselective intramolecular photocycloaddition of enone 5 to construct the congested core of the molecule. The photocycloaddition substrate was prepared through technology for the construction of carboalkoxycyclopentenones previously reported from these laboratories. Regioselective cyclobutane fragmentation and further functionalization of the photoadduct 4 provided the key pentacyclic intermediate. Acid-catalyzed rearrangement and epoxide opening were key transformations in the production of ginkgolide B from the pentacyclic intermediate.

Totalsynthese von natürlichem α‐Tocopherol. 1. Mitteilung. Herstellung bifunktioneller, optisch aktiver Synthesebausteine für die Seitenkette mit Hilfe mikrobiologischer Umwandlungen

Abstract: Total Synthesis of Natural α-Tocopherol. I. Preparation of Bifunctional Optically Active Precursors for the Synthesis of the Side Chain by Means of Microbiological Transformations Our concept for a new total synthesis of natural α-tocopherol includes the synthesis of a corresponding (3 R, 7 R)-configurated C15 side chain to be built up by using twice an optically active C5 unit together with an achiral C5 end part. (S)-3-methyl-γ-butyrolactone (11) and (S)-2-methyl-γ-butyrolactone (9) represent suitable bifunctional C5-precursors for this purpose. These two key compounds have been prepared by fermentative transformation including the enantioselective hydrogenation of the double bond of ethyl-4, 4-dimethoxy-3-methylcrotonate (5) by bakers yeast (yielding 11 after ester hydrolysis and cyclization of the fermentation product) and (E)-3-(1′, 3′-dioxolan-2′-yl)-2-buten-1-ol (8) by the fungus Geotrichum candidum (yielding directly 9).