Nicolaou cyclisation

The Buszek (—)-octalactin A synthesis is notable for its useage of the Corey-Nicolaou thiopyridyl ester7 protocol for saturated eight-mem-bered lactone construction. Prior to this synthesis, no eight-membered lactone ring had ever been prepared in high yield from the cyclisation of a saturated hydroxy carboxylic acid precursor. This reaction therefore broke important new ground in the arena of complex natural product synthesis. 

An impressive application of an aldehyde-oxime coupling was reported by Nicolaou in their studies on the total synthesis of the complex natural product diazonamide A (see Chapter 7, Section 7.4).29,30 Naito31 and Skrydstrup32 have reported impressive applications of the heteropinacol cyclisation for the stereoselective synthesis of the azepine ring of the PKC-inhibitor balanol (see Chapter 7, Section 7.4). 

An elegant application of the oxidation of 2-aminofurans has been described by Nicolaou and co-workers (02JA2190, 02JA2202) in model studies directed towards the total synthesis of CP molecules. In this study, the isolable iminobutenolide 80 is formed by cyclisation of the alkoxide 79 (Method B, Section II.B.l.b). Without a stabilising substituent on the ring the equilibrium favours the imine 80 rather than the amine 81 (Scheme 16). However, it is postulated that there is sufficient 2-ami -nofuran in equilibrium for this to be rapidly oxidised to the hydroperoxide 83. At this stage, the final product is determined by the reaction conditions. In strongly acidic conditions, tautomerism to the amine 85 and hydrolysis rationalises the formation of the isolated anhydride 88. Under weakly acidic conditions, formation of... 

Macrolides and Related Compounds.- The total synthesis of amphoteronolide B (166) and amphotericin B (167) has been reported in a series of papers by Nicolaou s group.The method uses the phosphonate-based olefination of (164) with (165) to form the basic carbon skeleton which is cyclised by an intramolecular phosphonate-based olefination. A Wittig reaction of the ylide (168) is a key step in the synthesis of the cytotoxic macrocycle riccardin C (169). 

Ring closing metathesis is a fundamental part of the strategy for the synthesis of Brevetoxin subunits employed by Clark and Kettle <97TL123>. This approach, complementary to that of Nicolaou and co-workers <96JA1565>, involves cyclisation of 26 to 27 by molybdenum catalysis. Yields of over 90% have been achieved The approach may also useful in the preparation of the 6,6-cyclic ethers, but not for 6,8-cyclic ethers of the brevetoxins. An alternative system for the latter has been proposed <97TL127>. 

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