Sachio Ishimoto

Prostaglandin chemistry—V : Synthesis of new prostaglandin synthons; 4(R)-(+)- and 4(S)-(−)-t-butyldimethylsiloxycyclopent-2-en-1-one

Abstract Optically active prostaglandin intermediates, 4( R )-(+)- and 4( S )-(−)-hydroxycyclopent-2-en-1-one derivatives, were synthesized from 3( R ),5( R )-diacetoxycyclopent-1-ene, 3( R )-acetoxy-5( R )-hydroxycyclopent-1-ene and 3( S ),5( S )-dihydroxycyclopent-1-ene obtained by microbiological hydrolysis of 3,5-diacetoxycyclopent-1-ene. The absolute configurations of all these compounds were determined by the exciton chirality method and the induced CD method. The optical purities were determined by NMR measurements of the diastereomeric esters of a versatile optically pure acid, (+)-α-methoxy-α-trifluoromethylphenylacetic acid.

Structure and synthesis of batatasins, dormancy-inducing substances of yam bulbils

Abstract Batatasin, which occurs in dormant bulbils of yams ( Dioscorea batatas Decne.) and induces dormancy in this organ has been shown by spectrometric analysis and synthesis to be 3,3′-dihydroxy-5-methoxy-bibenzyl.

Prostaglandin chemistry—IV : Microbiological kinetic resolution and asymmetric hydrolysis of 3,5-diacetoxycyclopent-1-ene

Abstract A 1:1 mixture of cis- and trans-3,5-diacetoxycyclopent-1-ene (1) was asymmetrically hydrolysed by bakers yeast to give trans-3(R)-acetoxy-5(R)-hydroxycyclopent-1-ene (R-2a) and S-predominant 3,5-dihydroxycyclopent-1-ene (3) accompanied by trans-3(R),5(R)-diacetoxycyclopent-1-ene (R-1a). The optical activities on the products were found to be dependent on the difference of the enzymatic hydrolytic rate among cis-, trans(S,S)- and trans(R,R)-3,5-diacetoxycyclopent-1-ene. The asymmetric hydrolysis was also investigated on wheat germ lipase, citrus acetyl esterase, and the lipase prepared from Aspergillus niger.

Biological activity of 1α,24-dihydroxycholecalciferol; A new synthetic analog of the hormonal form of vitamin D

It is well established [l] that vitamin Da must be hydroxylated on C-25 in the liver and subsequently on C-l in the kidney before it can carry out its functions in the intestine and bone. The resulting metabolite, lo,25dihydroxycholecalciferol (lc~,25-(OH)~-Da)~ is the presently known most potent and rapidly active analog of vitamin Da and is considered to be the hormonal form of the vitamin. Among many synthetic analogs, la-hydroxycholecalciferol (lo-OH-Da) has the approximately equivalent activity of lc~,25-(OH)~Da, in promoting intestinal calcium transport, bone mineral mobilization and curing rickets [2]. However, we have recently found [3] that la-OH-Da has a very high toxicity. LD,e-Values for

Synthesis of active forms of vitamin D. Part IX. Synthesis of 1α,24-dihydroxycholecalciferol

24-Oxocholesterol (1)(readily available from fucosterol) was converted by three steps into 1α,24ξ-dihydroxycholesterol (4). From the corresponding triacetate (5), 1α,24ξ-dihydroxycholecalciferol (9) was prepared via the 5,7-diene (8). The C-24 epimers of compound (4) were resolved by silica gel column chromatography of the monohydroxydibenzoates (7), and were separately transformed into the corresponding 1α,24-dihydroxycholecalciferol epimers.

Prostaglandin chemistry—VIII : Synthesis of optically active 7-oxoprostaglandins

Abstract Regiospecific α-acylation of β-alkenylated enolates generated by conjugate addition of lithium organocuprates to α,β-unsaturated ketones is described. Several new 7-oxoprostaglandin analogues, 7-oxoprostaglandin E 1 ( 18 ), 11-deoxy-7-oxoprostaglandin E 1 ( 23 ), and their 15-epi enantiomers 17 and 22 , were synthesized by conjugate addition-acylation method. From optically active 4( R ) -t - butyldimethylsiloxycyclopent - 2 - en - 1 - one ( R - 11 ), 7-oxoprostaglandin E 1 ( 18 ) was synthesized. Determination of the absolute configuration of 11-deoxy-7-oxoprostaglandin E 1 ( 23 ) and its 15-epi enantiomer ( 22 ) on the basis of CD study is described. Successful acylation of β-alkenylated lithium copper enolates with reactive acylating agents such as thiol esters and N-acyl imidazole as well as acyl halides is described.

A New Desulfurization Method: Application to the Synthesis of 11-Deoxyprostaglandin E2

Abstract Alkylation at carbon attached to sulfur of α-phenylthio or α-alkylthioketones, or reductive-alkylation of α-phenylthioketones provided a new regiospecific alkylation method of ketones.1,2 In these procedures, desulfurization was effected either by reduction with lithium in liquid ammonia1,2 or by use of Raney Ni-W-2.2 Recently, buffered sodium amalgam method has been reported to be effective for desulfurization of β-ketosulfides as well as for desulfonylation of aryl alkyl sulfones.3 We wish to report here that desulfurization of α-phenylthioketones was achieved by treatment of the ketones with zinc and chlorotrimethylsilane. This observation would lead to a facile synthesis of α-substituted ketones.

Biological activity assessment of 25-hydroxyvitamin D3-26,23-lactone in the rat

A new metabolite of vitamin D3 has been isolated from the plasma of chickens, rats and pigs given large doses of vitamin D3 and identified as 25-hydroxyvitamin Ds-26,23-lactone (25OH-Da-26,23-lactone) [l-3]. Four possible diastereoisomers of 25OH-Da26,23-lactone have been synthesized [4-91; they have been directly compared to the natural 25OH-Da-26, 23-lactone by high pressure liquid chromatography. The stereochemical configurations of the natural 25-OH-D,-26,23-lactone at C-23 and C-25 positions were determined to be 23(S) and 25(R), respectively [9,10]. 23(5)25Dihydroxyvitamin D3 [23(S)25(OH),Da] is a far better substrate for production of 25-OH-Ds-26,23-lactone than is 25,26_dihydroxyvitamin Ds (25,26-(OH),Ds) [ 11].23(,!7)25@)26&ihydroxyvitamin D3 [23(5)25@)26-(OH)sDs] is a better substrate than 23(5)25-(OH),D, in the biosynthesis of the 25-OH-Da-26,23-lactone [ 121. Therefore, the 25-OH-Ds-26,23-lactone may be biosynthesized from 25-OH-D3 by way of 23@)25-(OH),D, to 23(S)25(R)26-(OH),D,. 2.1. Compounds We synthesized 25-OH-D3 and lo,25-(OH)2Ds as in [ 13].25-OH-Da-26,23-Lactone was isolated and purified from the serum of rats given large doses of vitamin D3 as in [lo].

Effect and metabolism of 1α,24‐dihydroxyvitamin D3 in hepatectomized rats

It is well established that vitamin D3 undergoes metabolic conversion before exerting its biological effects [l-3]. The liver produces 25hydroxyvitamin Dj (25OH-Ds), which the kidney then converts to la,25dihydroxyvitamin Ds (la,25-(OH)2-D3) and 24,25dihydroxyvitamin D3 (24,25-(OH),-Ds). The bulk of experimental evidence suggests that lar,25(OH)2-Ds is a major hormonally active form of vitamin Ds, responsible for increasing intestinal absorption of calcium and phosphorus, enhancing bone resorption, and preventing rickets [l-3]. In contrast, the role of 24-hydroxylation and functions of the resulting metabolites remain still obscure. In a previous report, we demonstrated that la,24dihydroxyvitamin D3 (lc~,24-(OH)~-Ds), a synthetic analog of la,25(OH)2-Ds, has a potent activity in

Prostaglandin chemistry VI. Synthesis of 8-methoxycarbonylprostaglandins

Cyclopentenon (I) reagiert mit den Lithium-cupraten (II) nach anschliesender Umsetzung mit Chlorkohlensaureester (III) zu Mischungen der Substitutionsprodukte (IV) und (V), aus dem Tetrahydropyranyloxy-cyclopentenon (VI) entstehen die beiden Substitutionsprodukte (VII) und (VIII).