Prins cyclizations: labeling studies and application to natural product synthesis.

The first syntheses of two natural products, catechols 1 and 2, isolated from Plectranthus sylvestris (labiatae), are reported. Oxygen-18 labeling studies support the proposed intermediacy of a stabilized benzylic cation in the acid-promoted cyclization of an aldehyde and benzylic homoallylic alcohol possessing an electron-rich aromatic ring. In contrast, with an electron-deficient aromatic ring the pathway via a benzylic cation is only minor. [reaction: see text]

Oxonia-cope rearrangement and side-chain exchange in the Prins cyclization.

[reaction: see text] Evidence is presented here for the mechanism of the Prins cyclization of benzylic homoallylic alcohols, which shows that the outcome of the reaction is dependent upon the substituents on the aromatic ring. The presence of an electron-rich aromatic ring favors an oxonia-Cope rearrangement yielding a symmetrical tetrahydropyran as the major product formed via a side-chain exchange process. In contrast, with electron-deficient aromatic rings the expected 2,4,6-trisubstituted tetrahydropyran is formed.

Stereoselective synthesis of 4-hydroxy-2,3,6-trisubstituted tetrahydropyrans.

[reaction: see text] Reaction of homoallylic alcohols with aldehydes in the presence of TFA gives, after hydrolysis of the ester, 4-hydroxy-2,3,6-trisubstituted tetrahydropyrans with the creation of three new stereocenters in a single-pot process. By varying the aldehyde component, a variety of functionalized side chains are installed at C-2. The utility of this approach is extended to the enantioselective synthesis of tetrahydropyrans with >99% ee.

Glucuronidation of steroidal alcohols using iodosugar and imidate donors.

We report a study of the glucuronidation of a number of important steroidal secondary alcohols. The alcohols studied are androsterone 7, epiandrosterone 8, 17-acetoxy-androstane-3alpha,17beta-diol 9, 11alpha-hydroxyprogesterone 10, and 3-benzoylestradiol 11. These were first glucuronidated using the Schmidt trichloroacetimidate method with variations in acyl substituent (viz. derivatives 2 and 3), Lewis acid catalyst and order of addition. The results are contrasted with those obtained using our recently described glycosyl iodide donor 4, catalysed either by N-iodosuccinimide (NIS) or various metal salts.