Synthesis of structural variants of phospholipids: inhibition of phospholipase A2

The First Total Synthesis of (±)-Cyclophostin and (±)-Cyclipostin P: Inhibitors of the Serine Hydrolases Acetyl Cholinesterase and Hormone Sensitive Lipase

“…In addition, cyclophostin and the cyclipostins are probably biosynthetically related to A-factor 3 and the virginiae butanolides, 4 and the PLA 2 inhibitor 4 . 5 …”

“…In addition, cyclophostin and the cyclipostins are probably biosynthetically related to A-factor 3 and the virginiae butanolides, 4 and the PLA 2 inhibitor 4. 5 The significance of cyclophostin and the cyclipostins is due in part to their unique structures and the enzymes they inhibit. Interest in AChE has re-emerged due its role as a therapeutic target for Alzheimer's disease, 6 myasthenia gravis, 7 and glaucoma, 8 whereas HSL is a therapeutic target for type II diabetes.…”

“…The cyclipostins 2 are phosphate esters of long chain lypophilic alcohols of various lengths and structures, and all are potent inhibitors of hormone sensitive lipase (HSL). In addition, cyclophostin and the cyclipostins are probably biosynthetically related to A-factor 3 and the virginiae butanolides, and the PLA 2 inhibitor 4 …”

“…The hydroxyl was phosphorylated using dimethyl bromophosphate, prepared in situ by reaction of trimethyl phosphite with bromine, to give the phosphate 7 (Scheme ). The phosphorylated butyrolactone 7 was deprotonated with 1 equiv of LiHMDS in THF, and the resulting enolate was acylated with acetyl chloride. , Initially, mixtures of the acetyl lactone 14 and the enolacetate 13 were observed, so an excess of acetyl chloride was added to ensure the complete acylation giving enolacetate 13 in 65% yield as a mixture of two geometrical isomers. The geometrical isomers could be separated, but were generally carried through to the next step as a mixture.…”

Syntheses and Structure−Activity Relationships of Novel Apio and Thioapio Dideoxydidehydronucleosides as Anti-HCMV Agents

“…Treatment of (()-9 with LiHMDS at -78 °C followed by trapping of the enloate with trimethylsilyl chloride at room temperature gave the silyl enol ether, which without isolation was treated with phenylselenenyl bromide at -78 °C to give the desired (()-10a as a major product (80%) and the undesired (()-10b as a minor product (10%) after silica gel column chromatography. 13 The major formation of (()-10a was achieved because the phenylselenenyl group was added from the opposite side to the bulky TBDPS group as reported by Campbell 12 and Chu. 13 In addition to the explanation of the stereochemistry of the phenylselenenyl group by steric effect, a 1 H NOE experiment was employed to confirm the configuration of the phenylselenenyl group in (()-10a and (()-10b.…”