Chemical macrolactonizations

Lipases also catalyze the intramolecular transesterification (lactonization) of hydroxy esters. Macrolactonization of a racemic hydroxy ester in the presence of PSL provided the corresponding (R)-lactone (Figure 6.22). This compound is the naturally occurring enantiomer of the pheromone produced by the merchant grain beetle [70]. Chemical macrolactonizations require high dilution to minimize... 

Various a-methylenemacrolides were enzymatically polymerized to polyesters having polymerizable methacrylic methylene groups in the main chain (Fig. 3, left). The free-radical polymerization of these materials produced crosslinked polymer gels [10, 12]. A different chemoenzymatic approach to crosslinked polymers was recently introduced by van der Meulen et al. for novel biomedical materials [11]. Unsaturated macrolactones like globalide and ambrettolide were polymerized by enzymatic ROP. The clear advantage of the enzymatic process is that polymerizations of macrolactones occur very fast as compared to the chemically catalyzed reactions [13]. Thermal crosslinking of the unsaturated polymers in the melt yielded insoluble and fully amorphous materials (Fig. 3, right). 

Since tylosin is composed of tylonolide (macrolactone aglycone ring) and three attached sugars having several chemically reactive hydroxyl groups, it is... 

Paquette, L.A., Barriault, L., and Pissamitski, D. 1999. A Convergent Total S>nfiiesis of the Macrolactone Disaccharide Toxin (-)-Polycavernoside A. Journal of the American Chemical Society 121(18), 4542-4543. 

White, J.D, Blakemore, P.R., Browder, C.C., Hong, J., Lincoln, C.M., Nagorny, PA., Robarge, L.A., and Warthop, DJ. 2001. Total Synthesis of fiie Marine Toxin Polycavemoside A via Selective Macrolactonization of a Trihydroxy Carboxylic Acid. Journal of the American Chemical Society 123(35), 8593-8595. 

Nishida. A.. Yagi, K., Kawahara, N., Nishida, M., and Yonemitsu, ()., Chemical modification of erythromycin A. Synthesis of the C1-C9 fragment from erythromycin A and reconstruction of the macrolactone ring. Tetrahedron Lett., 36, 3215, 1995. 

As discussed earlier, the low intrinsic reactivity and high chemical stability of alkenyltins can be exploited in devising intramolecular alkenyl-alkenyl coupling particularly in the synthesis of cyclic natural products (Sect in.2.18). MaCTOcarbocycles including cyclic ketones and macrolactones have been synthesized by this coupling reaction as shown in Scheme 51. 

Lactide is efficiently polymerized by chemical catalysts based on tin(II) octonoate, zinc powder or zinc lactate,and aluminum based catalysts. However, thus far, the synthesis of polylactide (PLA) has proved difficult using lipase catalysts. In contrast, lipase-catalyzed polymerization of macrolactones... 

Chemical substances that act as chemical signals, in several organisms especially in insects, consist of macrolactone structures. These compounds, called as semiochemicals [29], are classified into pheromones and allelochemicals. 

Pheromones. The term pheromone [30] was coined by Karlson and Liischer [31] and these are the chemical signals used in individuals of the same species. Ferrulactones la (Figure 6.2) and 26-30 (Figure 6.11) are some representative examples of pheromones containing macrolactonic stractures [32]. 

Verbalactone 139 is a novel C2 symmetric macrocycUc dilactone, isolated from the roots of Verhascum undulatum possessing antibacterial activity [95]. It has 1,7-dioxacyclododecane moiety in its ring system and its first chemical total synthesis was reported by Sharma and Reddy [96] The two appropriately protected segments, acid 135 and alcohol 136, were prepared as shown in Scheme 6.23 and coupled by esterification and macrolactonization by the Yamaguchi method. 

TE domain is able to catalyze the macrocyclization of oo-hydroxy fatty acid ethyl esters to afford 17- to 28-membered lactones [35]. One would hope that in the future a rather general TE domain will be identified or optimized via directed evolution, which could compete with the chemical Yamaguchi macrolactonization. 

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