Lactones, unsaturated macrocyclic

Strategies for stereoselective synthesis of molecules with remote stereoge-nic centers across a double bond of fixed configuration in particular, for synthesis of heterocycles, especially unsaturated macrocyclic lactones 99JCS(P1)1899. 

The confomiational preferences and stereoselective reactions of a number of macrocyclic systems have been studied. The stereochemical results have been explained on the basis of the model of local conformer control. The epoxidation of a macrocyclic alkene containing the substitution pattern (21) provides a single epoxide having the stereochemistry (22). A macrocycle containing a l,S-diene system adepts the local confoimation (23) that is iree of torsional strain epoxidation of (23) from the less hindered side fiimishes the syn-diepoxide (24). The MCPBA epoxidations of the unsaturated macrocyclic lactones (25) and (2Q are stereoselective (equations 9 and 10). In the epoxidation of (26) six new chiral centres are introduced the reaction product is a 20 1 1 mixture of triepoxides. The tiiepoxide (27) is closely related to the C(9)-C(23) segment of monensin B. 

Intramolecular olefination of the phosphonates (184) and (186) has been used as the final step in syntheses of (+j-jolkinolides (e.g. 185)108 and the antitumour, antibiotic asperlin (187),109 respectively. In the latter case this confirms the stereochemistry of asperlin as (65,7/ ). A new synthesis of ( )-a,p-unsaturated macrocyclic lactones by intramolecular Wittig reaction of [Pg.356]

Such ring systems occur in many natural products of pharmacological interest. The same catalyst system was also successfully used for the RCM of an ester unsaturated in both the acid and alcohol fragment. Thus, the 5-heptenyl ester of 10-dodecenoic acid gave an unsaturated macrocyclic lactone (7) which, on hydrogenation afforded the natural product exaltolide (1,15-pentadecanolide), a perfume ingredient (Eq. 18). 

A useful route to 14—16-membered a,jS-unsaturated macrocyclic lactones from their corresponding co-iodoalkyl-propiolate esters under PhsSnH/AIBN-mediated conditions has been described by Baldwin s group (equation 24). As starting materials, bromides and selenides were found to be inferior to the corresponding iodides. Cyclizations were both... 

Cucujoides. Group of unsaturated macrocyclic lactones with 12 or 14 carbon atoms identified as pheromones of the saw-toothed grain beetles of the genera Cryptolestes and Oryzaephilus. Some of these compounds, which occur in differing mixtures in the different species, are chiral and species-specific. Enantiomer ratios have also been observed, see also ferra-lactone II. 

Naturally occurring organoleptically important lactones are mainly saturated and unsaturated 7- and -lactones, and to a lesser extent macrocyclic lactones. The occurrence of these types of lactones reflects their ready formation from natural acyclic precursors. 

The main feature of tin to hthium exchange is the preservation of the alkene stereochemistry, which was already demonstrated in 1964 . In conjunction with the easy access to stereodefined alkenyltins, this feature has been extensively exploited for synthetic purposes such as the construction of prostaglandins side chains and unsaturated fatty acids ° ° , the syntheses of a macrocyclic lactone , brefeldin cerulenin... 

Phosphonoacetate cycHzation. Intramolecular cyclization of keto phosphonates can be used for construction of macrocyclic a, -unsaturated lactones. Stork s laboratory found that use of lithium isopropoxide or lithium hexamethyidisilazide in THF containing 1% HMPT minimized formation of cyclic dilactones. Use of sodium or potassium counterions was much less satisfactory. An example is shown in equation (I). 

Maurer, B., and Grieder, A. (1977). (Z)-5-Tetradecen-14-olide, a new macrocyclic lactone, and two unsaturated straight chain acetates from ambrette seed absolute. Helv. Chim. Acta 60, 1155-1160. 

Pyrolysis, at 520 °C, of simple macrocyclic lactones (seven-membered or greater) affords high yields of open-chain, oj-unsaturated carboxylic acids a six-membered transition state has been proposed " (Scheme 9). Presumably the high temperature of this reaction precludes its application to more complex substrates. Similar unsaturated acids can be obtained by a novel cleavage of 1-tri-methylsiloxybicyclo[ ,l,0]alkanes using lead(iv) tetra-acetate in acetic acid (Scheme 10). 

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