Macrocydic lactone

The photochemistry of a,p nsaturated ketones has attracted much attention and is still a field cld of current interest. 1/Numer-ous examples of such photochemical transformations are well-documented for cyclic enones and dienones, including both cycloaddition ructions and rearrangements. For example, cyclopentenones / and/readily rearrange to cyclopropyl ketenes upon irra/idiation. Recently, the related cyclohexadienone/butadienyl ketene rearrangement has been shown to be a highly useful tool in the synthesis of natural products and macrocydic lactone /... 

The term macrolide was introduced to denote the class of substances produced by Streptomyces species containing a macrocydic lactone ring (27). 

Enzymatic polycondensation ttf a dicarboxylic add and a died has been reported using lipase from Candida cyUndracea, Pseudomonas and Porcine pancreas [34]. Competitk>n between linear polye r and macrocydic lactone formation was observed depei ing on the reactitm temperature. 

Furstner, A., Guth. O.. Rumho, A., and Seidel, G. (1999) Ring closing alkyne metathesis. Comparative investigation of two different catalyst systems and application to the stereoselective synthesis of olfactory lactones, azamacrolides, and the macrocydic perimeter of the marine alkaloid nakadomarin A. y. Am, Chem. Soc., 121, 11108-11113. 

In an approach to chlorothricolide, Ireland and Varney formed the C15-C16 bond using an Ireland-CIaisen rearrangement of a macrocydic aUylic lactone (Scheme 4.91) [84]. The stereoselectivily at the a<arboxylic acid stereocenter was not an issue, since the carboxyl group was later exdsed under radical conditions. The alkene was formed soldy as the T-isomer. 

On the other hand, the Mitsunobu reaction [28], an exceptional alcohol activation protocol, was also used for the preparation of macrocydic molecules [29]. Mitsunobu demonstrated the potential of lactoni2ation in the alternative total synthesis of 19 (Scheme 5.5) [30]. Among the many researchers employing this strategy for the preparation of cyclic molecules, it is notable that Meyers has recently accomplished the total synthesis of 9 utilizing this lactone linkage methodology (Scheme 5.6) [31]. 

This method offers a useful alternative to more typically employed Yamaguchi lactonization and RCM-mediated macrocydization methods. 

In spite of the living character of the anionic polymerization of PL, it was revealed that in the case of p-substituted p-lactones or medium-size cyclic esters (LA and CL) this process suffers from various side reactions such as chain transfer to monomer, racemization, segment exchange, or formation of macrocydic esters. " Finally, it has been concluded that in the so-called coordination-insertion (pseudoanionic) polymerization, initiated with covalent metal alkoxides (R MtOR c. where Mt is Zn, Al, Sn, Ti, etc.), these side reactions can be kinetically suppressed or even eliminated. Correlation of the selectivity parameters, defined as the ratio of rate constants of propagation and transfer (fep/fetr). with the reactivity of active species (fep) showed that these polymerizing systems conform to the reactivity-selectivity principle. ... 

Marshall, J.A., Crooks, S.L., and DeHolF, B.S. (1988) Cembranolide total synthesis macrocydization of (a-alkoxyaHyl)stannane-acetylenic aldehydes as a route to cembrane lactones. J. Org. Chem., 53, 1616-1623. 

H "The overall plan was derived using the strategy of antithetic analysis and depended on the tactic of generating the macrocydic unit by lactonization. Another major strategic element in the present approach is the use of sixmembered cyclic intermediates to establish and confirm the stereorelationships required for the C(l) to C(9) segment." (Corey, 1978) [6] ... 

The carbonylative macrocydization using acyl chlorides and diloroformates as substrates represents an interesting tool for the synthesis of cyclic ketones, lactones, a,/3-unsaturated esters. A complementary approach is based on the carbonyl insertion reaction with carbon monoxide and subsequent cross-coupling as exemplified by the approach to the core structure of Phomactins C and D, with an alkyne-enoltriflate carbonylative coupling as the key macrocydization step [131] (Scheme 6.17). 

As a typical example of this type of ROP-that of e-caprolactone, as initiated by an alkoxide function-is shown in Scheme 2.2 [1, 2]. Here, the alkoxide initiator reacts with the lactone at its carbonyl carbon, and this reaction leads to the formation of an alkoxide at the propagating chain end, which successively reacts with another lactone molecule. However, this propagating step is usuaUy accompanied by side reactions, mostly represented by the terminal alkoxide back-biting of the ester linkage in the main chain of the formed polyester. This back-biting reaction gives the monomer as well as macrocydic oligomers. 

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