Prostaglandin lactones

Di Marzo, V., Minardi, C., Vardaro, R. R., Mollo, E., and Cimino, G., Prostaglandin F-l, 15-lactone fatty acyl esters a prostaglandin lactone pathway branch developed during the reproduction and early larval stages of amarine mollusc, Comp. Biochem. Physiol., 101B, 99, 1992. 

The reaction of vinyloxiranes with malonate proceeds regio- and stereose-lectively. The reaction has been utilized for the introduction of a 15-hydroxy group in a steroid related to oogoniol (265)(156]. The oxirane 264 is the J-form and the attack of Pd(0) takes place from the o-side by inversion. Then the nucleophile comes from the /i-side. Thus overall reaction is sT -StM2 type, in the intramolecular reaction, the stereochemical information is transmitted to the newly formed stereogenic center. Thus the formation of the six-membered ring lactone 267 from 266 proceeded with overall retention of the stereochemistry, and was employed to control the stereochemistry of C-15 in the prostaglandin 268[157]. The method has also been employed to create the butenolide... 

The p-phenylbenzoate ester was prepared to protect the hydroxyl group of a prostaglandin intermediate by reaction with the benzoyl chloride (Pyr, 25°, 1 h, 97% yield). It was a more ciystalline, more readily separated derivative than 15 other esters that were investigated. It can be cleaved with K2CO3 in MeOH in the presence of a lactone. ... 

The lactone A was also used as starting material in the synthesis of the primary prostaglandins via an allylic substitution-semi-pinacolic rearrangement sequence (Ref. 2). 

The Baeyer-Villiger oxidation is a synthetically very useful reaction it is for example often used in the synthesis of natural products. The Corey lactone 11 is a key intermediate in the total synthesis of the physiologically active prostaglandins. It can be prepared from the lactone 10, which in turn is obtained from the bicyclic ketone 9 by reaction with m-chloroperbenzoic acid (MCPBA) " ... 

In addition to its other properties, interest in the potential use of the vasodilative properties of prostaglandin El, alprostadil ( ), has led to several conceptually different syntheses.For this purpose, the classic Corey process has to be modified by reversing the order of addition of the side chains to allow for convenient removal of the unwanted double bond in the upper side chain. For example, Corey lactone is protected with dihydropyran (acid catalysis), reduced to the lactol with diisobutyaluminum hydride, and then subjected to the usual Wittig reaction to give intermediate This is... 

A particularly flexible and novel entry into prostaglandins and analogs, either by RCAM (463—>464) or by the intermolecular variant ACM (462+466 -+467) from a common intermediate (462), is outlined in Scheme 93 [190]. Prostaglandin E2-1,15-lactone (465), an ichthyotoxic compound produced by a marine nudibranch for defense purposes, was produced in Fiirstner s laboratory along the RCAM-based sequence 462 463—>464-+465. Alternatively, the... 

The Baeyer-Villiger reaction has found considerable application in the synthesis of prostaglandins. One common pattern involves the use of bicyclo[2.2.1]heptan-2-one derivatives, which are generally obtained by Diels-Alder reactions. For example, compound 10 is known as the Corey lactone and has played a prominent role in the synthesis of prostaglandins.237 This compound was originally prepared by a Baeyer-Villiger oxidation of 7-(methoxymethyl)bicyclo[2.2.1]hept-5-en-2-one.238... 

Recently, a novel class of prostaglandin derivatives, PG-1,15-lactones (Fig. 1) of both E [16] and F [17] series, has been reported to occur in the opisthobranch mollusc Tethys fimbria, along with smaller amounts of some of the corresponding PGs. Some lactones were present mainly in the mucous secretion and dorsal appendages known as cerata, while others were more abundant in the mantle. Fatty acid esters of PGF-1,15-lactones (C9 and Cu) were found only in T. fimbria eggmasses and reproductive glands (ovotestis). The structural variety of the lactones and the data on their distribution in the body... 

Fig. 1. Prostaglandin 1,15-lactones and prostaglandins isolated from Tethys fimbria...

Di Marzo V, Cimino G, Sodano G, Spinella A, Villani G, A novel prostaglandin metabolic pathway from a marine mollusc prostaglandin 1,15-lactones. 7th Internation Conf, on Prostaglandins and related compounds, 28 May-1 June 1990, Florence, Italy, p 13... 

Cimino, G. Crispino, A. Di Marzo, V. Spinella, A. Sodano, G. (1991) Prostaglandin 1,15-lactones of the F series from the nudibranch mollusc Tethys fimbria. J. Org. Chem., 56,2907-11. 

---