Abstract
Since their isolation almost 20 years ago, the callipeltosides have been of long standing interest to the synthetic community owing to their unique structural features and inherent biological activity. Herein we present our full research effort that has led to the synthesis of these molecules. Key aspects of our final strategy include 1) synthesis of the C1–C9 pyran core (5) using an AuCl3-catalysed cyclisation; 2) formation of C10–C22 vinyl iodide (55) by sequential bidirectional Stille reactions and 3) diastereoselective union of these advanced fragments by means of an alkenylzinc addition (d.r.=91:9 at C9). The common callipeltoside aglycon (4) was completed in a further five steps. Following this, all three sugar fragments were appended to provide the entire callipeltoside family. In addition to this, D-configured callipeltose B was synthesised and appended to the callipeltoside aglycon. The 1H NMR spectrum of this molecule was found to be significantly different to the natural isolate, further supporting our assignment of callipeltoside B (2).
Highlights
Natural product synthesis continues to provide an attractive platform for the discovery of new synthetic methods and further elaboration of novel synthesis pathways
Synthesis of pyran 5 a) Double dithiol conjugate addition approach to C1–C9 pyran 5: Our synthetic effort began with the preparation of the pyran aldehyde 5 from (R)-configured Roche ester 7
At the beginning of our study we committed to the ambitious union of pyran aldehyde 5 and vinyl iodide 6 (55 with a TBS protecting group) by a diastereoselective alkenylmetal addition with subsequent Yamaguchi macrocyclisation to complete the common callipeltoside aglycon
Summary
Natural product synthesis continues to provide an attractive platform for the discovery of new synthetic methods and further elaboration of novel synthesis pathways. These investigations began with sulfone 41 a (Scheme 8) which, in combination with Cs2CO3 in THF/DMF (3:1) at room temperature gave vinyl iodide 55 in moderate yield (54 %), but disappointingly as a mixture of Z/E isomers favouring the Z form (6:1) (Table 1, entry 1).
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