Plexaura homomalla Esper

P. homomalla35'39 coffee brown in color, highly branched bush like the Caribbean soft coral, found in abundance is extraordinarily rich in PGA2, methyl ester (29) (up to 2% of dry weight) or the 15-epimer depending on subspecies.2915-epi PGA2 (28) and its diester (29) isolated from the air dried cortex in the yield 0.2% and 1.3% respectively,29 were epimeric with potent mammalian hormone at allylic hydroxyl centre C-15. They were, however, devoid of the dramatic blood pressure lowering (dog) effect of PGA2 (12) itself. Their function like that of other compounds occurring in the gorgonian remains speculative. The diester (29) was isolated by chromatography of the crude hexane extract in benzene/ethyl acetate on silicic acid. High resolution mass spectrometry established its composition as C23H34O5 and demonstrated the loss of acetic acid and the even-mass fragment, C6H10CO2Me. The IR spectrum of (29) showed carbonyl absorptions at 1735 cm- , typical of simple ester, and at 1710 cm- compatible with a conjugated cyclopentenone moiety. Hydrogenation of the diester (29) and the acid (28) over Palladium gave the hexahydro-diester (30) and the hexahydro acid (31), respectively. The compound (30) showed no hydroxyl absorption in the infrared and carbonyl absorption only at 1735 cm-. The ultra violet absorption maximum at 300 nm confirmed the presence of cyclopentanone group in (30).

The mass spectrum of (30) showed the loss of the even mass fragment. C6H10CO2Me, suggesting the presence of this side chain in the a position of the cyclopentanone, as well as the loss of acetic acid and fragment C8H15 suggesting the presence of an acetate bearing side chain. The NMR spectrum

of (29) showed two sharp methyl singlet at 8 1.98 (acetate) and 3.61 (methoxy) and a third methyl group as a perturbed triplet characteristic of an alkyl chain terminus at 8 0.89. A pair of double doublets at 8 6.12 and 7.42 (J = 2 Hz, 6.2 Hz) indicated the presence of conjugated double bond (C-10, 11) and their multiplicity clearly indicated a single substituent at C-12. By decoupling experiments it was shown that the H-10 and H-11 protons are coupled to the one proton singlet at 8 3.22 (H-12) which was also coupled with H-13 and H-14 protons. Thus, the prostaglandins (28) and (29) isolated from gorgonian were found epimeric with C-15 in PGA2 (12).

All known natural mammalian prostaglandins have the ^-configuration at the C-15 asymmetric centre.35 Weinheimer and Spraggins29 had reported the non mammalian"prostaglandins, 15- epi- PGA2 (28) and its acetate methyl ester (29) isolated from the Caribbean soft coral Plexaura homomalla which had ^-configuration at C-15. Schneider et al40 reinvestigated the samples of P. homomalla and found that some forms of soft coral contained instead of the (R)-prostaglandins, esterified derivative of (155)-PGA2 (32) and (155)-PGE2 (33) identical with the prostaglandins derived from mammalian sources.

In some single specimen of this gorgonian, both (15R) and (155), prostaglandins were also found. The (15R) and (155) forms of these two prostaglandins, differ slightly in silica gel TLC, using the AIX polarity system, the (15R)-isomer being less polar, so that preliminary identification in coral extraction can be made. The origin of primary prostaglandins in marine organisms raises many intriguing biochemical questions. Bundy et al41 have reported the conversion of both (155)-(32) and (15R)-(29) PGA2 into biologically important primary prostaglandins, PGE2 (3) and PGF2 (6). (15R)-PGA2 methyl ester (29) was treated with methane sulphonyl chloride in pyridine and the resulting crude 15-mesylate was solubilized in acetone-water to give modest yields of the C15 inverted product, (155)-PGA2 methyl ester. Acetylation of the product in acetic anhydride/pyridine gave (32) and thus, ultimately to PGE2 (3) and PGF2 (6). Plexaura homomalla var. (R) and var. (5) are thus both suitable sources of (coral) prostaglandins useful in the synthesis of PGE2 and PGF2. From the (5) variety PGE2 can be obtained in three steps and PGF2 in four steps.


During the chromatographic purification of (155)-PGA2 from the gorgonian P. homomalla var. (5) a new natural prostaglandin identified as 5-trans-

PGA2, was isolated.42 This compound was less polar than PGA2 on silver nitrate impregnated silica gel. Column chromatography of crude (15S)-PGA2 on Amberlite-15 Ag+ form or on silver nitrate impregnated silica gel gave a minor component to which the structure (15S)-15-hydroxy-9-oxo-5-trans-10,13-trans-protatrienoic acid C5-trans-PGA2 (34) was assigned. Content of the trans-isomer usually ranged between 5 and 15% of the PGA2. 5-trans-PGA2 was an oil, Amax 217 nm (e 9050); [a]D 128° (CHCl3); molecular ion peak at 478.2998 for TMS derivative (calcd for C26H46O4Si2 478.2932) and mass spectrum was found to be identical with PGA2.

Irradiation of prostaglandin E2 (3) in oxygen free benzene-methanol solution with 3500 /light for 24 hr in a Rayonet photochemical reactor in the presence of diphenyl sulphide gave, after careful chromatography on acid-washed silica gel a 22% yield of 5-trans-PGE2, m.p. 75-7 °C (which was identical with the material derived from P. homomalla). In a similar fashion and in similar yield, crystalline 5-trans-PGF2p and 5-trans-PGF2 were prepared from the corresponding 5-cis-prostaglandins and were also found identical with the coral derived compounds. Re-examination of the extracts of P. homomalla var. (S) prior to hydrolysis showed that while small amount of the free acids are present however, the 5-trans isomer was predominantly in the form of its 15-acetate methyl ester. It is not yet clear whether the presence of trans-isomer represents biosynthetic formation from 5-trans-arachidonic acid endogenous to P. homomalla or a subsequent transformation product of 5-ds-PGA2.

PGF2-9-O-acetate methyl ester

Weinheimer and Spraggins29 had discovered that the Caribbean gorgonian Plexaura homomalla (Esper, Plexauridae) contained remarkable quantities (in excess of 2% dry weight) of 15-epi and 15-normal prostaglandin PGA2 (12). Smaller quantities of PGB2 (14) and PGE2 (3) were also found in the gorgolean. Groweiss and Fenical43 investigated the extracts of P. homomalla collected in the Bahama Islands and isolated a simple prostaglandin derivative characterized as PGF2a-9-O-acetate methyl ester (35). PGF2a-11-O-acetate methyl ester (36), an acetate positional isomer of 35 had been isolated as a natural product from the Red Sea soft coral Labophytom depressum.44

Prostaglandin (35) was isolated as viscous oil that was analyzed for C23H38O6. The compound showed spectral characteristic for multiple ester linkage (1750 cm- br) and hydroxyl functionalities (3400 cm- br). Consideration of XH and 13C NMR data, and specifically the results of COSY analysis allowed the complete structure (35) to be assigned. The 15S1 configuration in (35) was assigned based upon the similar l3C NMR shift of C-13, C-17 in comparison with those reported for compound (37). A careful literature survey revealed that (35) had been prepared as a synthetic intermediate.45 However, this is the first report of the ester occurring as a natural product.

13,14-Dihydro and 13,14-cis-unsaturated prostaglandins Enzymatic hydrolysis of prostaglandin esters in the coral P. homomalla obtained from Cayman islands, gave a mixture from which PGA2 (12); 5,6-trans-PGA2, PGE2 (3) and traces of PGE3 had been isolated chromatographically. Further separation by silica gel chromatography of fractions less polar than PGA2 had disclosed the presence of other prostaglandins of which, 13,14-cis-PGA2; 15-acetate (38) and 13,14-dihydro-PGA2 acetate methyl ester (39) were characterized.46

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