Monensin, lactonization

Isonitriles Four-membered lactones Monensin derivatives... 

Individual polyethers exhibit varying specificities for cations. Some polyethers have found appHcation as components in ion-selective electrodes for use in clinical medicine or in laboratory studies involving transport studies or measurement of transmembrane electrical potential (4). The methyl ester of monensin [28636-21 -7] i2ls been incorporated into a membrane sHde assembly used for the assay of semm sodium (see Biosensors) (5). Studies directed toward the design of a lithium selective electrode resulted in the synthesis of a derivative of monensin lactone that is highly specific for lithium (6). 

Unsaturated -lactone 34 adopts a well-defined conformation and provides a suitable platform for the introduction of the stereogenic center at C-24 (monensin numbering). Catalytic hydrogenation of the carbon-carbon double bond in 34 takes place preferentially from the less hindered side of the molecule and provides an 8 1 mixture of stereoisomers in favor of 35 (100% yield). Cleavage of -lactone 35 with concentrated hydriodic acid at 130°C, followed by treatment of the resultant iodide 36 with triphenylphosphine, completes the synthesis of intermediate 19. 

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. 

Figure 2 (a) Classic biosynthesis of monensin A (7) (b) novel monensins (16) (c) monensinyl N-acetylcysteamine thioester (14) (d) triene lactones... 

A total synthesis of the monensin lactone is summarized in Scheme 50. The crucial point of this synthesis is the hetero Diels-Alder reaction of triethylsilyloxy diene (179) with aldehyde (180), carried out with 10 mol % of Yb(fod).i to give the syn Diels-Alder cycloadduct (181) as the only isomer. Compound (181) is treated with HF in pyridine and MeOH to obtain ketone (182), which is converted into the monensin lactone (183). 

The lactones shown in the Table include several representatives of recognized or potential value as starting materials in natural product synthesis. Lactone 1 is a precursor of grandisollactone 3 of some pyrethroids, lactone 6 of some prostaglandins, and lactone 7 of multistriatin, methynolide and monensin. ... 

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