On the Origin of Siphonariid Polypropionates: Total Synthesis of Caloundrin B and Its Isomerization to Siphonarin B

Abstract

Enantioselective synthesis of the enantiomer of caloundrin B was achieved by strategic aldol coupling of an enantiopure trioxaadamantanecontaining ketone with a racemic pyrone-containing aldehyde via kinetic resolution. In the presence of imidazole, ent-caloundrin B is cleanly isomerized to ent-siphonarin B confirming the proposed structure and absolute configuration for caloundrin B and establishing that it is a plausible biosynthetic product from which siphonarin B and baconipyrones A and C can originate.

Total Synthesis of Muamvatin

“…In this regard, Ward et al developed methodologies for fast, easy, and selective preparation of propionate synthons via the thiopyran route to polypropionates and successfully disclosed total synthesis of several polypropionate natural products. [8][9][10][11] With these examples in hand, research was directed towards the synthesis of putative linear precursor of muamvatin and studying its cyclization modes.…”

“…Such considerations suggest that seemingly different polypropionates might originate from a common linear or thermodynamically unstable precursor. 10,11,23 Extensive experimentation has shown that polyketides are synthesized in nature by multifunctional enzymes called polyketide synthases (PKSs). 25 Such enzymes are capable of condensing a malonic acid derivative with an activated thioester and simultaneous decarboxylation of the malonic acid.…”

Marine natural products

“…891 Enantioselective synthesis of ent-caloundrin B (Siphonaria zelandica) 892 conrmed the proposed relative and absolute conguration and in the presence of imidazole was found to isomerise to ent-siphonarin B. 893 The absolute congurations of the bis-g-pyrone polyproprionate onchidione (Onchidium sp.) 894 and two methanolysis products have been assigned by analysis of X-ray diffraction data and TDDFT calculated ECD spectra.…”

Application of Chiral 2-Isoxazoline for the Synthesis of syn-1,3-Diol Analogues

“…1,2 (3R)-β-Hydroxy-δ-lactone or its open-ring equivalent (3R)-syn-3,5-dihydroxypentanoic acid, is a common structure in naturally occurring mevastatin (or compactin), lovastatin or closely related statins, and synthetic statins. Either syn-or anti-1,3-diol could be prepared from enantiomerically pure β-hydroxy ketone via β-hydroxy directed carbonyl reduction in Evans' 3 or Prasad's [4][5][6][7][8][9][10][11] method. Narasaka-Prasad reduction of the δ-hydroxy-β-keto-ester derived from a β-hydroxy ester [12][13][14][15][16][17][18][19][20][21][22][23] is widely used to prepare t-butyl (3R)-3,5-O-isopropylidene-3,5-dihydroxyhexanoate (Scheme 1a) [24][25][26][27][28][29][30][31][32][33][34][35][36][37] , which is a building block for synthetic statins, [38][39][40][41] though enzymatic synthesis [42][43][44][45]…”