Rapid and slow hydroxylators of seminal E prostaglandins

Oliw, Ernst H.; Johnsen, Ø.

doi:10.1016/0005-2760(88)90294-9

Cited by 14 publications

(13 citation statements)

References 23 publications

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“…Irrespective of the nature of the fungal hydroxylating enzymes, it is remarkable that their sites of attack, C-18 and -19, are identical with the sites of hydroxylation of natural prostaglandins by mammalian enzymes (37)(38)(39)(40)(41)(42)(43). Furthermore, the absolute stereochemistry at C-19 in the human metabolite 19-hydroxy-PGB has been identified as (R) (44), identical to that observed in the present study.…”

Section: Discussionsupporting

confidence: 83%

Hydroxylation of prostanoids by fungi. Synthesis of (−)-15-deoxy-19-(R)-hydroxy-PGE₁ and (−)-15-deoxy-18-(S)-hydroxy-PGE₁

Holland¹,

Brown²,

Chenchaiah³

et al. 1990

Can. J. Chem.

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A series of racemic substituted cyclopentanones, with alkyl groups corresponding to the upper prostanoid side chain and (or) the lower prostanoid side chain without the C-15 alcohol, has been synthesized. Using a steroid template for the prostanoid molecule as a basis for selection, fungi capable of hydroxylating steroids have been used to biotransform the prostanoid substrates. The predominant products were hydroxylated at the prostanoid C-18 and C-19 positions. The hydroxylations were enantioselective, with excesses in the range 10-60%, and in most cases the predominant configuration corresponded to that of the natural prostanoids. The stereochemistry of the C-19 hydroxyl group was found to be R by degradation of products to methyl 6-acetoxyheptanoate and comparison of that material with a resolved sample, obtained via crystallization of the brucine salt of ethyl 6-phthaloxyheptanoate. Hydroxylation at C-18 gave the S configuration of alcohol. Hydroxylation at prostanoid C-15 was observed, but in all cases this was accompanied by other reactions. Hydroxylation of Rhizopus arrhizus has been used in a preparation of ( Chem. 68, 282 (1990). On a synthttist une sCrie de cyclopentanones substitukes ractmiques portant des groupements alkyles correspondant a la chaine laterale prostano'ide supCrieure et (ou) a la chaine lathale prostanoide infkrieure ne portant pas la fonction alcool en C-15. Utilisant comme base de sClection un gabarit stCroi'dal pour representer la molCcule prostanoi'de, on a fait appel a un champignon capable d'hydroxyler les stkroides pour effectuer la biotransformation des substrats prostanoldes. Les produits principaux sont les prostano'ides hydroxylCs en positions C-18 et C-19. Les hydroxylations sont CnantiosClectives, avec des excks de l'ordre de 10-60%, et, dans la plupart des cas, la configuration prCdominante correspond a celle des prostanoYdes naturels. En se basant sur une dkgradation des produits en 6-acCtoxyheptanoate de mCthyle et sur une comparaison de ce produit avec un Cchantillon rtsolu, obtenu par cristallisation du sel de brucine du 6-phtaloxyheptanoate d'ithyle, on a dCmontrC que la stCrCochimie du groupement hydroxyle en C-19 est R. L'hydroxylation en C-18 foumit un alcool de configuration S. On a observt une hydroxylation en C-15 du prostano'ide; toutefois, cette reaction est toujours accompagnee par d'autres reactions. On a fait appel une hydroxylation par le Rhizopus arrhizus pour la prkparation des (-)-15-dCsoxy-19-(R)-hydroxy-PGWI et (-)-15-dCsoxy-18-(S)-hydroxy-PGW,.

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Section: Discussionsupporting

confidence: 83%

Hydroxylation of prostanoids by fungi. Synthesis of (−)-15-deoxy-19-(R)-hydroxy-PGE₁ and (−)-15-deoxy-18-(S)-hydroxy-PGE₁

Holland¹,

Brown²,

Chenchaiah³

et al. 1990

Can. J. Chem.

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“…The two most abundant PGs are 19R-hydroxy-PGE 1 and 19R-hydroxy-PGE 2 (24). Although PGE compounds are present in 100,000-fold higher concentration in human seminal fluid (0.4 ± 0.1 mM) than in any other body fluids (24,25), the physiological functions of seminal fluid PGEs remain a mystery, in spite of research efforts since the mid-1930s. It is puzzling that these huge amounts of PGs occur in semen, as PGs have powerful local effects on the pregnant uterus and are even used as drugs to induce cervical ripening and abortion.…”

Section: Unorthodox Routes (I): Novel Routes For Prostanoid Biogenesimentioning

confidence: 99%

Unorthodox routes to prostanoid formation: new twists in cyclooxygenase-initiated pathways

Serhan

Oliw²

2001

J. Clin. Invest.

135

103

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“…There is a marked inter-individual variation in the amount of PGE and 19-hydroxy-PGE compounds in normal human seminal fluid (8,9). This may be due to variable expression of CYP4F8 or due to isoforms with reduced enzyme activity.…”

Section: Fig 3 Lc-ms Analysis Of Pg Compounds Formed During Incubatmentioning

confidence: 99%

Identification of CYP4F8 in Human Seminal Vesicles as a Prominent 19-Hydroxylase of Prostaglandin Endoperoxides

Bylund

Hidestrand

Ingelman‐Sundberg

et al. 2000

Journal of Biological Chemistry

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Rapid and slow hydroxylators of seminal E prostaglandins

Cited by 14 publications

References 23 publications

Hydroxylation of prostanoids by fungi. Synthesis of (−)-15-deoxy-19-(R)-hydroxy-PGE₁ and (−)-15-deoxy-18-(S)-hydroxy-PGE₁

Hydroxylation of prostanoids by fungi. Synthesis of (−)-15-deoxy-19-(R)-hydroxy-PGE₁ and (−)-15-deoxy-18-(S)-hydroxy-PGE₁

Unorthodox routes to prostanoid formation: new twists in cyclooxygenase-initiated pathways

Identification of CYP4F8 in Human Seminal Vesicles as a Prominent 19-Hydroxylase of Prostaglandin Endoperoxides

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Rapid and slow hydroxylators of seminal E prostaglandins

Cited by 14 publications

References 23 publications

Hydroxylation of prostanoids by fungi. Synthesis of (−)-15-deoxy-19-(R)-hydroxy-PGE1 and (−)-15-deoxy-18-(S)-hydroxy-PGE1

Hydroxylation of prostanoids by fungi. Synthesis of (−)-15-deoxy-19-(R)-hydroxy-PGE1 and (−)-15-deoxy-18-(S)-hydroxy-PGE1

Unorthodox routes to prostanoid formation: new twists in cyclooxygenase-initiated pathways

Identification of CYP4F8 in Human Seminal Vesicles as a Prominent 19-Hydroxylase of Prostaglandin Endoperoxides

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Hydroxylation of prostanoids by fungi. Synthesis of (−)-15-deoxy-19-(R)-hydroxy-PGE₁ and (−)-15-deoxy-18-(S)-hydroxy-PGE₁

Hydroxylation of prostanoids by fungi. Synthesis of (−)-15-deoxy-19-(R)-hydroxy-PGE₁ and (−)-15-deoxy-18-(S)-hydroxy-PGE₁