Hydroxy-y-lactones

These products can be reduced by sodium borohydride in combination with nickel(II) chloride to the corresponding 8-hydroxy--y-lactones in 90-95% yield.1... 

Monobactams have been investigated as p-lactamase inhibitors <98CHE1308, 98CHE1319>. The ketene-imine route to P-lactams was used to obtain 1,3,4-trisubstituted derivatives with high trans selectivity. The enolate from 4-hydroxy-y-lactone reacted with the imine (Ar CH NAr ) to give 59, vdiich cyclized in the presence of lithium chloride at low temperature to yield 60. The compounds were assayed for cholesterol absorption inhibition and 61 (R = = OH, R = F) was found to be a potent inhibitor of 3-hydroxy-3-... 

In analogy to the /f-hydroxy-y-lactones, / -acetamino-y-lactones can also be a-alkylated by means of their dianions, which again are mostly prepared by the addition of 2 equivalents of LDA. 

Ethyl-1,4-dimethylazulene Eudesma-4(14),ll(13)-dien-12-oic acid,8P-hydroxy-, y-lactone Chamazulene Isoalantolactone... 

In addition, Cushman and co-workers121 reported the synthesis of a 1-hydroxyethylene dipeptide with a Pro moiety at the C-terminus using the reaction between an a-amino aldehyde and a lithium cyclopentanone enolate. Matternich and Liidi 22 described the synthesis of a y-(aminoalkyl)-a-hydroxy-y-lactone starting from the addition of an a-amino aldehyde to a pyruvate enolate. 

A recently published full account of another synthesis [69] of the same alkaloid starting from the /rans-cinnamic ester 264 represented a different approach (ACD -> ACDB) to ( )-lycorine (Scheme 42). An intramolecular Diels-Alder reaction of 264 in o-dichlorobenzene furnished the two diastereomeric lactones 265 (86%) and 266 (5%) involving the endo and exo modes of addition respectively. The transposition of the carbonyl group of 265 to 267 was achieved by reduction with lithium aluminium hydride, followed by treatment of the resulting diol with Fetizon s reagent, which selectively oxidised the less substituted alcohol to give isomeric 5-lactone 267. On exposure to iodine in alkaline medium 267 underwent iodolactonisation to afford the iodo-hydroxy y-lactone 268. The derived tetrahydropyranyl ether... 

Figure 2. Examples of Various Lactone Moieties in Annonaceous Acetogenins an a, p-Unsaturated-y-lactone [Annonin I (4)], a C(4)-Hydroxylated a, P-Unsaturated-y-lactone [Bullatacin (5)], a Rearranged Acetonyl Butanolide [Bullatacinone (6)], and a Saturated p-Hydroxy-y-lactone [Itrabin (7)].

Garcia et alf have described the synthesis of a-hydroxy- y-lactones by the alkylation of protected cyanohydrin anions with epoxides. 

Valeric acid, a-ACETYL- -CHLORO-7-HYDROXY-, y-LACTONE, 31, 1 5-HYDROXY-3-METHYL, 5-LACTONE,... 

Lactone formation, by intramolecular condensation of a-acetoxy-ketones in strongly basic media, has been examined systematically. Lithium di-isopropylamide in ether is effective as the base conditions must be chosen according to the reactant. Scheme 8 illustrates successful reactions, which afforded either the /3-hydroxy-y-lactone or the butenolide, depending upon the ease of adoption of the conformation necessary for elimination of water. The method appears to be limited to tertiary a-acetoxy-ketones. 

Diketene similarly reacts readily with tributyltin oxide in THF at room temperature47 to give the stannyl 3-stannyloxybut-3-enoate which rearranges to the 2-enolate this enolate will then give an ene reaction with an aldehyde,48 or react with an alkyl halide,49 followed by decarboxylation, providing a route to ketones, enones, and ketoaldehydes. Similar reactions with bromomethyl P- or y-lactones result in the formation of P-hydroxy-y-lactones or y-hydroxy-5-lactones. 

The catalytic system has been efficiently applied to the sequential [4 + 2] cycloaddition/ring opening reaction to afford highly enantioenriched a-hydroxylated carbonyl derivatives in excellent yields (Scheme 10.7). A variety of important classes of compounds, such as a-hydroxy-y-lactone, a-hydroxy-y-lactam, factor Xa inhibitor,... 

Dihydro-2(3//) furanone 4-Hydroxy- y-lactone 4-Deoxytetronic acid... 

An aqueous solution of glyoxylic acid reacts with cyclopentadiene to provide a-hydroxy-y-lactones the more acidic the solution, the faster the reaction (Scheme 13) [68]. Thus at pH 0.9 (2.25 M glyoxylic acid solution in water) the reaction is complete after 90 min at 40 °C providing a 83 % yield of a-hydroxy-y-lactones. In the case of cyclohexadiene, the reaction is complete after 2 days at 90 °C in water, compared to 21 h at 120 °C for the reaction with butyl glyoxylate in neat conditions (Scheme 13). These results show that it is possible to exploit the die-nophilic character of a carbonyl group in water in spite of its quasi total hydration. Pyruvaldehyde, glyoxal, and even ketones like pyruvic acid, also react with dienes in water [69]. 

Valeric acid, ol-acetyl-S-chloro-y-hydroxy-, y-lactone, 31,1 Vanillic acid, 30,101,103 Vanillin, 30, 102, 104 Veratraldehyde, 31, 58 Vinyl acetate, 30, 106 Vinyl caprate, 30,108 Vinyl caproate, 30,108 Vinyl caprylate, 30,108 Vinyl 10-hendecenoate, 30,108 Vinyl laurate, 30,106 Vinyl myristate, 30,108 Vinyl oleate, 30, 108 Vinyl palmitate, 30,108 Vinyl pelargonate, 30, 108 Vinyl stearate, 30,108 Vinyl undecylenate, 30,108... 

An aqueous solution of glyoxylic acid reacts with cydopentadiene to provide a-hydroxy-y-lactones (Eq. 4) the more acidic the solution, the faster the reaction [41]. 

Asymmetric synthesis of hydroxy-y-lactones Asymmetric dihydroxyiation of fi, y- and y, 5-unsaturated esters is accompanied by spontaneous lactonization to hydroxy y-lactoncs, generally in 96-98% ee, which can be increased to 100% by a single crystallization. 

Calcium chloride a-Hydroxy-y-lactones from / -hydroxy aldehydes... 

Their structures were mainly determined by spectral studies using EI-MS, IR, H-NMR, NOE, and CD spectra (75). They consist of a main spiroether moiety, corresponding to 1-oxaspiro[5. 5]undec-4-ene-8-one ring system, (including seven asymmetric centers and possessing a (Z)-olefin, a mefa-substituted phenol, and a P-ketocarboxylic acid functions) and a P-hydroxy-y-lactone moiety. Oscillatoxin Ds are present as esters of both moieties. On the other hand, aplysiatoxins are present as macro bis-lactones including a spiroacetal. We are interested in the relationship between oscillatoxins and aplysiatoxins from a biosynthetic point of view. 

Hydroxy-y-lactone moieties, segment Cl and segment C2, are known compounds whose syntheses have been reported. Therefore, we followed the reported methods and could readily synthesize both segment Cs. 

Epoxy-carbonsauren bzw. deren Lactame lassen sich in schwach saurem Medium in Hydroxy-y -lactone bzw. 2-Aminomethyl-2-buten-4-olide umwandeln z.B. ... 

The intermediate hydroxy-y-lactone probably has undergone acyl transfer to the more stable trans disubstituted hydroxy-8-lactone. The p-bromophenyl-urethane derivative of 75, mp 196-198°C, (TTC negative) was utilized in determination of the structure and of the relative configuration by X-ray analysis (153). 

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