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A review, cyclization reactions in natural product synthesis of 4-9 membered and larger rings were discussed. [on SciFinder (R)]

Pestalotiopsin A is a structurally unique, caryophyllene-type sesquiterpene which has shown immunosuppressive activity and cytotoxicity in preliminary assays. A stereocontrolled approach to the functionalised 2-oxabicyclo[3.2.0]-heptane core of pestalotiopsin A is described. This constitutes the first synthetic studies on pestalotiopsin A. Our approach includes a samarium(II)-mediated 4-exo-trig cyclisation and a trans-lactonisation process triggered by the addition of alkylytterbium reagents to a cyclobutanone intermediate. Further manipulation provides access to advanced intermediates which are excellent precursors for the future construction of the final ring of the target.

A samarium(II)-mediated 4-exo-trig cyclization in which a remote stereocenter serves to control the facial selectivity of the cyclization is described. The apparent coordination of a tert-butyldimethylsilyl ether to the samarium center appears to give rise to the selectivity. The remarkable effect of the cosolvent, 2,2,2-trifluoroethanol, on the cyclization of this substrate, is also discussed. A stereoselective synthesis of the general class of gamma,delta-unsaturated aldehyde cyclization substrate is reported, and the utility of the cyclization is demonstrated in an approach to the fully functionalized core of pestalotiopsin A.

This study surveys the total community prescription use of benzodiazepine agents in Australia for the years 1990 and 1991. Also included is information on the utilisation of these agents on the Pharmaceutical Benefits and Repatriation Pharmaceutical Benefits Schemes (PBS/RPBS) over the period 1987 to 1991. The Australian data are from the Drug Utilization Subcommittee (DUSC) database, which is derived from two sources: the PBS/RPBS (subsidized prescriptions), and a national sample of Pharmacy Guild of Australia pharmacies (private and under-copayment general prescriptions). The data are converted to defined daily doses per 1000 inhabitants per day (DDD/1000/day) in accordance with the unit of measurement for drug utilisation studies approved by the World Health Organization. Benzodiazepine utilisation was 33.96 DDD/1000/day for 1990 and 29.31 DDD/1000/day for 1991. The four drugs listed on the Pharmaceutical Benefits Scheme, namely diazepam, oxazepam, nitrazepam and temazepam, constituted 82 per cent of the Australian market. The availability of government subsidy appears to influence benzodiazepine- prescribing behaviour. Benzodiazepine utilisation has been falling in recent years. The fall may be related to the impact of new guidelines and community awareness campaigns. There are major differences in the composition of the market between Australia and the Nordic countries.