A-hydroxy lactones

Perbenzoic acid gave a doubly unsaturated triol monobenzoate. Only two hydroxyl groups could be acetylated, and one was tertiary. The saturated triol reacted with lead tetracetate to give an a glycol. When reacted with chromic acid, it gave a hydroxy lactone. From these observations, Windaus and Gmndmann (11) described the correct stmcture for ergosterol (1). 

Treatment of a-iodo lactone (45) with triethylborane under oxygen atmosphere gives the corresponding a-hydroxy lactone (46), via a-lactone radical species. This reaction comprises of SH2 reaction by Ef on the iodine atom of a-iodo lactones, reaction of the formed a-lactone radical with molecular oxygen, and subsequent hydrogen-atom abstraction from the solvent to form alkyl hydroperoxide (ROOH). Finally, by the addition of dimethyl sulfide for the reduction of the peroxide, the corresponding a-hydroxy lactone is obtained (eq. 2.24) [58]. 

Camptothecin (CRT, 6, Figure 2.2) was first isolated from the Chinese ornamental tree Camptotheca acuminata Decne, also known as the tree of joy and tree oflove. It occurs in different plant parts such as the roots, twigs, and leaves. It is a member of the quinoline alkaloid group and consists of a pentacyclic ring structure that includes a pyrrole quinoline moiety and one asymmetric center within the a-hydroxy lactone... 

Hydroxylation of the sodium enolate of lactone (16) with (+)-( ) gives a-hydroxy lactone in 77% ee (eq 17). Kinetic resolution and asymmetric hydroxylation with (camphor-sulfonyl)oxaziridines has been applied to the synthesis of enantiomerically enriched a-hydroxy carbonyl compounds having multiple stereocenters, which may otherwise be difficult to prepare. Thus hydroxylation of the enolate of racemic 3-methylvalerolactone with substoichiometric amounts of (—)-(l) affords (25,3/J)-verrucarinolactone in 60% ee (eq 18) which on recrystallization is obtained enantiomerically pure. ... 

Asymmetric hydrogenation. a-Hydroxy lactones and yacetamino-P-hydroxy esters in chiral form are created from a,y-diketo esters and 4-acetamino-3-keto-4-alkenoic esters, respectively, on hydrogenation. 

The hydroxylation of lactones with (63a) or (+)-(114) usually affords a single diastereomeric a-hydroxy lactones resulting from approach of the oxidant from the sterically least hindered direction (Table 16). In one example, however, the diastereoselectivity proved to be strongly counterion dependent <93CJCi40i>. 

S) -( — )-2-Methyl-2-hydroxy-y-butyrolactone (176a) is a useful synthon for the asymmetric construction of acyclic tertiary a-hydroxy acids found in natural products such as the pheromone frontalin and mevalonolactone, the biosynthetic precursor of terpenoids and steroids. This compound is readily prepared from lactone (175) using the asymmetric enolate oxidation protocol and dimethoxy oxaziridine ( + )-(158) <95JOC6l48>. The a-hydroxy lactone (176b), isolated as the benzoate, was obtained in 84% ee and 70% yield. A single crystallization from ethyl acetate improved the ee to >94% (Equation (41)). 

The hydroxylation of the unsaturated lactone (107) by the treatment of its potassium enolate with the Davis oxaziridine afforded the a-hydroxy lactone (108) as a single diastereoisomer (Scheme 6) <92TL67l>. Evans et al. have examined the diastereoselection of the azidation reaction of the potassium enolate derived from the unsaturated lactam (109). The product (110) was formed in only moderate yield, and as a 1 1.4 mixture of diastereoisomers (Scheme 6) <92TL6859>. 

Camptothecin, the potent antitumor and antileukemic agent isolated from the stem wood of the Chinese tree Camptotheca acuminata Nyssaceae, has been the target of numerous chemical syntheses. The first successful synthesis of this unusual alkaloid, characterized by an a-hydroxy-lactone and a pyridone system fused to a five-membered ring, was reported by Stork and Schultz in 1971. A key feature of this synthesis is construction of ring E by a novel lactone annelation involving addition-cyclization of the carbonate of an 0 -hydroxy ester to the tetracyclic Q ,/3-unsaturated lactam (B). 

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