Highlights in Total Synthesis of Natural Products

A neat four-step synthesis of the triquinane sesquiterpene hirsutene (4) has been described, which features the novel iodotrimethylsilane induced rearrangement of the dione (1), to (2), as a key step. Reductive methylation of the enone (2) to (3),followed by Wittig methylenation then completed the synthesis.  

In a rather lengthy synthesis of the marine metabolite capnellene(12), Stille and Grubbs have highlighted the interesting 

Although a number of syntheses of the angular triquinane sesquiterpene isocomene (18) have now been published, the synthesis by Dreiding et al. is interesting since it features the sequential alkynone cyclisations (14)— -(15) and (16)——(17) as the two key 5-ring annulation reactions. In a new synthesis of the related sesquiterpene silphinene (23) intramolecular(2+2] photocycloaddition from (19) is first used to elaborate the tricycle (20), which on brief exposure to iodotrimethylsilane produces (21). Reduction of (21) to (22), and functional group elaboration then completed the 

The intramolecular cyclopropanation from (24) to (25), followed by regioselective reductive cleavage of (25) to (26) in the presence of sodium-liquid ammonia has featured in a new synthesis of 

Punctatin A (34), also known as antibiotic M 95464, is an unusual metabolite which has been isolated from the dung fungus Poronia punctata. An enantiospecific synthesis of (34) has now been described which features, amongst other things, use of the Norrish type II photoreaction viz (32)- -(33) to elaborate the cyclobutane ring 

The arene-olefin meta-photocycloaddition approach to triquinane natural products is further illustrated this year with a three-step total synthesis of ( )-silphinene (5) starting from 2-bromotoluene (1). Thus, irradiation of the arene-olefin (2) derived from (1) gave a 1 1 mixture of the photoadducts (3) and (4) in 70% yield. Regioselective reductive cleavage of the cyclopropane bond in (3), 

An interesting chelation-controlled regioselective ring enlargement, by means of an epoxide-carbonyl rearrangement, i.e. (8) - 

Photochemistry, in the shape of the de Mayo reaction, also features in a new synthesis of the linear fused triquinane hirsutene (20). Thus, photocycloaddition between dimedone and 2-methyl-cyclopent-2-enol was accompanied by spontaneous retro-aldolization of the intermediate adduct (17), leading to (l8a). McMurry coupling of the dione (l8b), derived from (l8a), followed by manipulation of the functional groups in (19) then led to (+)-hirsutene 

Reagen+s ij 160 Cj benzenejiijO iii,KOHjMeOH iv,CrOj,Me2CO vjPb(OAc), Cu(OAc vi, Me CuLi viij N H, KOH 

The last few years have witnessed a renaissance of interest in the use of carbon radical intermediates in the synthesis of all types of ring systems. A significant example of the power of this 

Most of the trends which were apparent in previous years have continued to manifest themselves. The feverish activity directed towards the synthesis of the hirsutane class of sesquiterpenes has not abated and other natural products containing annulated cyclopentane rings have also proved popular synthetic targets. In the field of steroid synthesis. Stork and his co-workers have developed an outstandingly elegant approach to 11-oxygenated steroids. 

Work concerned with providing solutions to the difficult stereochemical problems encountered in the synthesis of the macrolide and polyether antibiotics continues, and in this field pride of place must go to the total synthesis of erythromycin which has been completed by the collaborators of the late R. B. Woodward. 

The previously established biosynthetic relationship between fomannosin (1) and illudol (2) provides the key element in the strategy behind the total synthesis of (1) by Semmelhack and Tomoda. Thus a stereospecific Diels-Alder reaction provided (3) which was converted to (4) in several steps. Silyl ether cleavage brought about a spontaneous translactonization to yield (5) which was readily converted to (1). 

The upsurge of interest in the synthesis of natural products containing two or more fused cyclopentane rings shows no signs of abating. Three different reports of total syntheses of ( )-isocomene (6) have now appeared, two of 

Four syntheses of the related sesquiterpene, modhephene (9) have also been reported. One of these also proceeds via a [2 + 2]photocycloaddition route to give (7) followed by an acid-catalysed Cargill rearrangement to (8), which was converted to modhephene (9) by conventional methods. The bulk of the work in this area continues to be directed at the synthesis of sesquiterpenes of the hirsutane group. Details have appeared of the previously reported synthesis 

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Two further chapters deal with developments in the synthesis of saturated carbocycles (Chapter 7) and saturated heterocycles (Chapter 8) and the final chapter provides a summary of Highlights in Total Synthesis of Natural Products. A list of reviews on General and Synthetic methods is collected at the end of the Report. 

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