10.1021/acs.joc.9b03434
The study reports the first synthesis of cyclosiphonodictyol A (11) and its bis(sulfato) derivative (12) from the commercially available lactone (+)-sclareolide (17). The synthetic sequence involves 11 steps with a global yield of 46%. Key steps include the nucleophilic attack of a hindered tertiary alkoxide, a ring-closing metathesis reaction, and the Diels-Alder cycloaddition of a dienol acetate. The synthesis begins with the conversion of (+)-sclareolide (17) to alcohol 16, which is then converted to oxy-ester 21 using bromo ester 20 as an alkylating agent. The oxepane ring is formed via ring-closing metathesis of ester 21 to give ester 22. Subsequent transformations involve the conversion of ester 22 to ketone 14, followed by the construction of the aromatic ring through a series of reactions involving trans-1,2-bis(phenylsulfonyl)ethylene and isopropenyl acetate to form cycloadducts 24, which are then converted to acetate 25 and finally to phenol 13. Phenol 13 is oxidized to quinone 26 and subsequently reduced to cyclosiphonodictyol A (11). Compound 11 is then converted to its bis(sulfato) derivative (12) through successive treatments with pyridine-sulfur trioxide and Na2CO3. The synthesized compounds exhibit similar NMR data to the natural products, confirming their structures.
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