Caloundrin B and Funiculatin A: New Polypropionates From Siphonariid Limpets

Abstract

Two new polypropionates, caloundrin B (11), systematic name (1″R,2R,3″R,4R,5S,5″R,6S,-7″R,8″S,9″S,10″R)-2-(6′-ethyl-3′,5′-dimethyl-4′-oxopyran-2′-yl)-6-(5″-ethyl-7″-hydroxy-8″,9″,10″-trimethyl-2″,4″,6″-trioxatricyclo[3.3.1.13,7]dec-3″-yl)-5-hydroxy-4-methylheptan-3-one, and funiculatin A (12), systematic name (2ξ,1′S,4R,5′S,6′S)-2-(1′-ethyl-4′,6′,8′-trimethyl-2𔈀,9′-dioxabicyclo[3.3.1]nona-3′,7′-dien-3′-yl)-4,6-dimethylnon-6-en-3-one, have been isolated from Siphonaria zelandica and S. funiculata respectively. The structures of the new compounds were deduced by two-dimensional n.m.r. spectroscopy, particularly long-range 13C- 1H correlation spectroscopy (HMBC), by biosynthetic reasoning and by comparison with the known polypropionates denticulatin A (5), siphonarin B (8), muamvatin (9) and baconipyrone C (14). Information about the relative stereochemistry of the tricyclic ring system of (11) and the bicyclic ring system of (12) was deduced from coupling constant values, and by n.O.e. difference and NOESY experiments, and was confirmed by molecular modelling studies. The relative stereochemistry of the side chains and the absolute stereochemistry were inferred from biosynthetic comparison with the above known polypropionates, and by correlation of funiculatin A with denticulatin A (5) of known absolute stereochemistry. The stereochemistry at C10 of funiculatin A (position 2 of the non-6-en-3-one chain) could not be unambiguously determined. A third new polypropionate funiculatin B, epimeric with funiculatin A at C10, was isolated and partially characterized.

Total Synthesis of Muamvatin

“…23 Although, siphonariid mollusks are primitive in evolutionary terms, they are extraordinary architects of a variety of polypropionate natural products and regardless of their geographical locations, they produce similar polypropionate metabolites. 24 These polypropionates have been categorized into two classes.…”

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

“…Attempts to re-isolate 3 or isomerize siphonarin B (2) under acidic conditions to produce 3 were unsuccessful. 15 To date, there have been no further reports of isolation of caloundrin B (3) nor has its total synthesis been disclosed.…”

“…11,15,20 Considering that C-8 in 23 is stereochemically labile via keto-enol tautomerism, one epimer would produce siphonarin B (2) and the other would generate caloundrin B (3). In addition, the baconipyrones 4 and 6 could be artifacts of isolation coming from rearrangements on 2.…”

“…15 The structure of caloundrin B (3) was deduced by spectroscopic methods providing strong evidence for the presence of a γ-pyrone and the trioxaadamantane motif with the indicated relative configuration. The C-12 to C-21 fragment seemed to match with the same fragment present in baconipyrone C (6) (Figure 1.1).…”

“…9,15 Therefore, a convergent synthesis of 3 was proposed involving aldol coupling of the trioxaadamantane-containing ketone 95 with the γ-pyrone-containing aldehyde (±)-30. The proposed use of the racemic fragment (±)-30 for this strategy would require studies of methodology on the design of aldol reactions that proceed with kinetic resolution (vide infra).…”