Total synthesis of (+)-papulacandin D

Abstract

A total synthesis of (+)-papulacandin D has been achieved in 31 steps, in a 9.2% overall yield from commercially available materials. The synthetic strategy divided the molecule into two nearly equal sized subunits, the spirocyclic C-arylglycopyranoside and the polyunsaturated fatty acid side chain. The C-arylglycopyranoside was prepared in 11 steps in a 30% overall yield from triacetoxyglucal. The fatty acid side chain was also prepared in 11 steps in a 30% overall yield from geraniol. The key strategic transformations in the synthesis are: (1) a palladium-catalyzed, organosilanolate-based cross-coupling reaction of a dimethylglucal-silanol with an electron rich and sterically hindered aromatic iodide and (2) a Lewis base-catalyzed, enantioselective allylation reaction of a dienal and allyltrichlorosilane. A critical element in the successful execution of the synthesis was the development of a suitable protecting group strategy that satisfied a number of stringent criteria.

Synthesis of 5,6- and 6,6-Spirocyclic Compounds

“…A similar epoxidation-spirocyclization method has been used recently by Denmark et al [142,143] in their synthesis of papulacandin D, as well as in an independent study [144] toward papulacandin analogues (Scheme 69).…”

Nanocatalysts for Hiyama, Stille, Kumada, and Negishi C–C Coupling Reactions

“…8 The reasons for this increase in research directed toward nanocatalyzed C C couplings are several. First of all, C C couplings form one of the most significant classes of organic synthetic strategies, and they find application in the synthesis of materials as diverse as capparatriene (a drug used to treat leukemia), 9 tazarotene (an antiacne agent), 10 altinicline (effective for the treatment of Parkinson's disease and Alzheimer's disease), (+)-papulacandine D (an antifungal compound), 11 liquid crystals, 12 Light emitting diodes, organic conductors, 13 dendrimers, 14 supramolecular species, and so on. Second, nanomaterials represent a continuum between discrete atoms and macroscopic objects, and in doing so, possess unique physical, chemical, and electrical properties, which bestow upon them special catalytic abilities that may be harnessed for "green" chemical transformations under benign reaction conditions.…”

Disulfonimid‐katalysierte asymmetrische vinyloge und bisvinyloge Mukaiyama‐Aldolreaktionen

“…Weiterhin sind noch keine bisvinylogen Aldoladditionen entwickelt worden, die a,b,g,d-ungesättigte Ester in einem Schritt liefern könnten. [6] Hier beschreiben wir asymmetrische vinyloge Aldoladditionen, die durch unser kürzlich eingeführtes Disulfonimid 1 vermittelt werden. [7] Außerdem präsentieren wir die zuvor unbekannte Erweiterung von Mukaiyama-Aldolreaktionen hin zu einer bisvinylogen, e-selektiven und hoch enantioselektiven Variante.…”