Formal total synthesis of mandelalide A

Abstract

In this article the formal total synthesis of mandelalide A has been described in details. The highly convergent and flexible strategy developed for mandelalide A involved the construction of key building blocks ent-9 and 7, and their assembly to the target compound. For the synthesis and coupling of these building blocks, the Brown's crotylation, Sharpless asymmetric dihydroxylation followed by in situ Williamson type etherification, modified Prins cyclization, Masamune-Roush olefination and Heck cyclization were employed, the latter being crucial for the highly stereoselective formation of the macrocycle of mandelalide A. Initially, Julia Kocienski olefination, ring-closing metathesis reaction were investigated for the synthesis of the aglycone of the proposed structure of the mandelalide A, and found to be unsuccessful.

Progress toward the Synthesis of Pochonin J

“…Protection of the free alcohol in 15 as its tert-butyldiphenylsilyl (TBDPS) ether using the corresponding silyl chloride and Hünig's base (i-Pr 2 NEt) provided silyl ether 19 in excellent yield. Next, reduction of the Weinreb amide functional group employing diisobutylaluminum hydride (DIBALH) followed by Masamune-Roush olefination of the resultant aldehyde afforded ethyl enoate 20 in good overall yield for the two-step process [12] [13]. At this stage, we were primed to install the requisite stereochemistry at C(4).…”

Stereoselective Construction of (E,Z)‐1,3‐Dienes and Its Application in Natural Product Synthesis

“…In both cases, the reaction worked remarkably well. Recently, Ghosh published a full account displaying the setbacks they encountered for the macrocyclisation step, which proceeded through an ene‐ene ring closing metathesis (RCM) and E,Z ‐diene formation using the Julia‐Kocieński olefination (for other strategies used in the total synthesis of mandelalide A, see sections 2.2.1.5, 2.6.1, 2.10) [83] …”

“…Recently, Ghosh published a full account displaying the setbacks they encountered for the macrocyclisation step, which proceeded through an ene-ene ring closing metathesis (RCM) and E,Zdiene formation using the Julia-Kocieński olefination (for other strategies used in the total synthesis of mandelalide A, see sections 2.2.1.5, 2.6.1, 2.10). [83] Whiting reported the first synthesis of racemic phthoxazolin A by a strategy that relied on a series of Pd-catalysed reactions to stereoselectively forge the Z, Z,E-trienyl unit. [84] A Heck reaction under optimised, base-free conditions between a vinyl boronic ester (91) and a vinyl iodide (92) furnishes vinyl boronic ester intermediate 93 as the major product.…”

The Tetrahydrofuran Motif in Polyketide Marine Drugs

“…Amos B. Smith developed an anion relay chemistry (ARC) strategy [74] to synthesize the tetrahydrofuran and tetrahydropyran structural motifs which were joined by Yamaguchi esterification [75]. Intramolecular Heck cyclization [76], Sharpless asymmetric dihydroxylation [77] or Julia olefination [78] were also employed in other total syntheses.…”