Yuzhou Wang

Total synthesis of pamamycin-607☆

Abstract The macrodiolide antibiotic pamamycin-607 has been synthesized by coupling of the two hydroxy acid constituents using the Yamaguchi method. While the final lactonization with formation of the ester linkage between C(1) and the C(8′) oxygen proceeded with complete C(2) epimerization, the alternative ring closure involving the carboxylic acid of the smaller fragment and the hydroxyl group of the larger fragment yielded the target molecule.

Resolution of methyl nonactate

Abstract A straightforward resolution of racemic methyl nonactate has been achieved by chromatographic separation of the corresponding d -mandelates followed by chemoselective hydrolysis of the mandelate ester function. Bakers yeast reduction of the ketone derived from racemic methyl nonactate proceeded with high enantioselectivity to give (+)-8- epi -methyl nonactate and (−)-methyl nonactate as alternative building blocks for macrotetrolide synthesis but was less efficient for the production of the latter compound.

A General Access to Zaragozic Acids: Total Synthesis and Structure Elucidation of Zaragozic Acid D and Formal Syntheses of Zaragozic Acids A and C

The zaragozic acids or squalestatins have been isolated from various fungi. They are nanoto picomolar inhibitors of the squalene synthase of mammals and fungi and therefore, inhibit very efficiently the biosynthesis of cholesterol and show fungicidal properties. A few examples also inhibit ras-farnesyl protein transferase at nanomolar concentrations, which might be interesting for the development of antitumor agents. In more recent studies it was shown that these compounds can also cure prion-infected neurons and protect against prion neurotoxicity, as well as sensitize acute myeloid leukemia cells (AML) to radiochemotherapy. Almost all zaragozic acids share a highly oxygenated heterobicyclic core, whereas structural differences reside in the alkyl side chain at C1 and the ester side chain at C6. Due to their strong physiological effects and complex molecular structure, these natural products have stimulated enormous synthetic efforts, some of which have already culminated in several total syntheses of zaragozic acid A (1 a) and zaragozic acid C (1 b), 5] as well as the less oxygenated representative 6,7-dideoxysqualestatin H5. We recently communicated an efficient symmetry-based route to the 2,8-dioxabicycloACHTUNGTRENNUNG[3.2.1]octane derivative 4, which offers itself as a general building block for zaragozic acids by virtue of its functionality. Herein, we present the application of 4 to the first total synthesis of zaragozic acid D (1 c), which has also enabled the assignment of its hitherto unknown configuration at C4’ and C5’. In addition, we describe the utilization of 4 for a formal synthesis of 1 a and 1 b. Zaragozic acid D (1 c) is one of the most active ras-farnesyl protein transferase inhibitors in this natural product series with an IC50 of 100 nm. [8,9] A comparison with the structures of 1 a and 1 b suggested that the syn configuration in the alkyl side chain of these acids was most likely for 1 c as well. Retrosynthetically, compound 1 c was traced back to propargylic alcohol 2, which in turn could be prepared from terminal alkyne 3, which should be available from the hetero ACHTUNGTRENNUNGbicyclic compound 4 (Scheme 1).

Amino analogs of actic acids—synthesis and lactamization

Novel THF-amino acids were efficiently synthesized from actic acid methyl esters. The conformational restriction imposed by the 2,5-cis disubstituted tetrahydrofuran moiety is apparent from their facile cyclization to give medium-sized lactams.

Enantioselective Total Synthesis of 3β-Hydroxy-7β-kemp-8(9)-en-6-one, a Diterpene Isolated from Higher Termites

The first total synthesis of the title diterpene was accomplished starting from the Wieland-Miescher ketone. A diastereoselective sulfa-Michael addition enabled the generation of the delicate β,γ-unsaturated ketone moiety, while the tetracyclic kempane skeleton was readily constructed through domino metathesis.

Total Synthesis of the Neoclerodane Diterpene Salvinorin A via an Intramolecular Diels–Alder Strategy

A concise total synthesis of the neoclerodane diterpene salvinorin A from 3-furaldehyde is reported using two highly diastereoselective intramolecular Diels-Alder reactions (IMDA) as the key transformations.