A highly efficient, stereoselective oxyfunctionalization of unactivated carbons in steroids with dimethyldioxirane†

Iida, Takashi; Yamaguchi, Takeru; Nakamori, Ryusei; Hikosaka, Masahiro; Mano, Nariyasu; Goto, Junichi; Nambara, Toshio

doi:10.1039/b104938k

Cited by 33 publications

(38 citation statements)

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“…A comparison of the oxyfunctionalization of the 5β-steroids, 1 and 2, by the DMDO and DCP N-oxide / Ru(TMP)CO / HBr system revealed the following similarities and differences. As has been reported previously, 3,7 5β-hydroxylation in 5β-steroids is essential for both the oxidants. In addition, 17α-and 14α-hydroxylations are characteristic for DMDO oxidation, while 20S-hydroxylation and 15-ketonization are given by DCP N-oxide / Ru(TMP)CO / HBr oxidation.…”

Section: Resultsmentioning

confidence: 73%

“…The number and positions of oxygenation, as well as γ-lactone formation, were confirmed by the 1 H-and 13 C-NMR (Table 1) and GC-MS analyses, compared with those of analogous steroid derivatives reported previously. 3,8 In 5, the regioselective ketonization of the unactivated methylene carbon at C-15 in 1 was the sole example in this study, and may have occurred by successive oxidation of an intermediary 5β,15ξ-dihydroxy compound. 7 In 6, the formation of the γ-lactone derivative probably arises from intramolecular esterification between the 24-carboxyl group and 20S-hydroxyl group via a possible (20S)-3α-acetoxy-5β,20-dihydroxy intermediate, in analogy with the direct 20S-hydroxylation of 5β-cholestane.…”

Section: Resultsmentioning

confidence: 99%

“…1 Our previous papers have reported the utility of dimethyldioxirane (DMDO; see Figure 1) as an effective oxygen-donating reagent against unactivated carbons in 5β-steroids. [2][3][4] However, the use of DMDO appears to be limited to oxidizing C-20~-23 side-chain carbons in 5β-cholanoic acid derivatives. Meanwhile, a number of metalloporphyrins closely related to the iron porphyrin complex (heme) present in the active center of cytochrome P-450, has also been reported as attractive oxidant systems for oxidation reactions.…”

Section: Introductionmentioning

confidence: 99%

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A comparative study of remote oxy-functionalization of unactivated carbons in 5β-steroids by dimethyldioxirane and 2,6-dichloropyridine N-oxide / ruthenium-porphyrin / HBr

Iida¹,

Ogawa²,

Shiraishi³

et al. 2003

Arkivoc

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Remote oxy-functionalization of methyl 3α-acetoxy-and 3-oxo-5β-cholan-24-oates with 2,6-dichloropyridine (DCP) N-oxide catalyzed by (5,10,15,20-tetramesitylporphyrinate) ruthenium (II) carbonyl complex [Ru(TMP)CO] and HBr was compared with that with dimethyldioxirane (DMDO). Treatment of the 5β-steroids with DMDO afforded the corresponding 5β-and 17α-monohydroxylated and 5β,14α-and 5β,17α-dihydroxylated compounds. On the other hand, the corresponding 20S-mono-and 5β,20S-dioxygenated derivatives (as the γ-lactones), along with 5β-hydroxy compounds, were found to be the major oxidation products of the 5β-steroids with the DCP N-oxide / Ru(TMP)CO / HBr system. Both the reagents oxidized unactivated methine carbons stereoselectively, but the degree of regioselectivity depended upon the oxidants employed and the structure of the hydroxyl-protecting groups at C-3 (acetoxyl or carbonyl) of the substrates.

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Section: Resultsmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A comparative study of remote oxy-functionalization of unactivated carbons in 5β-steroids by dimethyldioxirane and 2,6-dichloropyridine N-oxide / ruthenium-porphyrin / HBr

Iida¹,

Ogawa²,

Shiraishi³

et al. 2003

Arkivoc

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“…A key intermediate, 3a,7b-diacetoxy-14a-hydroxy-5b-cholanoate (3a), was prepared in one-step from methyl ursodeoxycholate 3,7-diacetate (2a; methyl 3a,7b-diacetoxy-5b-cholan-24-oate) by remote-oxyfunctionalization of 2a with a freshly prepared CHCl 3 solution of dimethyldioxirane (DMDO). 16,17) The desired 14a-hydroxy derivative (3a) of 2a was isolated in 10% yield. Alkaline hydrolysis of 3a with 10% methanolic KOH, followed by acidification with 10% H 2 SO 4 yielded the 3a,7b,14a-trihydroxy acid 4.…”

Section: Resultsmentioning

confidence: 99%

“…HR-MS was also obtained on a JEOL JMS-700 mass spectrometer with an EI probe under the PIM. Methyl 3a a,7b b-Diacetoxy-14a a-hydroxy-5b b-cholan-24-oate (3a) This compound 3a was prepared from methyl ursodeoxycholate 3,7-diacetate 2a (8 g) according to the procedure described in a previous paper 17) ; yield, 840 mg, 10%. 3a a,7b b,14a a-Trihydroxy-5b b-cholan-24-oic Acid (4) A solution of the 14a-hydroxy ester 3a (480 mg) in 10% methanolic KOH (10 ml) was refluxed for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of 3.ALPHA.,7.ALPHA.,14.ALPHA.-Trihydroxy-5.BETA.-cholan-24-oic Acid: A Potential Primary Bile Acid in Vertebrates

Kakiyama

Iida

Goto

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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Chenodeoxycholic acid (CDCA, 3a,7a-dihydroxy-5b-cholan-24-oic acid) and cholic acid (CA, 3a,7a,12a-trihydroxy-5b-cholan-24-oic acid) are formed from cholesterol in the liver and are the dominant primary bile acids in many vertebrate species. CDCA may be considered the building block of all trihydroxy-bile acids and in many vertebrates one additional hydroxy group is added, either to the steroid nucleus or to the isopentanoic acid side chain.2) Such additional hydroxylation may occur either at any stage of an intermediate during bile acid biosynthesis or after the mature molecule has been synthesized. 6a-Hydroxylation of CDCA in the pig to give a 3a,6a,7a-trihydroxy acid (hyocholic acid) was reported by Haslewood and Sjövall.3) In the rat and mouse, 6b-hydroxylation results in the formation of 3a,6b,7a-trihydroxy bile acid (a-muricholic acid). 4) In more recent work, 1a-hydroxylation (vulpecholic acid) of CDCA was identified in the Australian opossum.5) The 1b-epimer 6) of this bile acid has been reported to be present in the bile of fruit pigeons and doves (Columbiformes) and in the human biological fluids from newborns and from adult patients with cholestatic liver diseases.7) The 4b-hydroxy derivative 8) of CDCA occurs in the biliary bile acids of patients with hepatobiliary diseases and in neonates and newborn infants. Hydroxylation at the C-5 (b-OH) position has been reported to occur in the biliary bile acids of the pheasant, 1) and 5b-hydroxylation of analogous nor-CDCA was demonstrated in hamster liver.9) The presence of the 3a,7a,15a-trihydroxy acid noted in the biliary bile acids of the marsupial and of the swan.1) In the most recent work, Hagey et al. 10) have reported the existence of the 3a,7a,16a-trihydroxy acid as a primary bile acid in many species of birds such as herons (Ardeidae), pelicans (Pelecanidae) and owls (Tytonidae).Hydroxylation on the side-chain of CDCA has also been reported. Haemulcholic [(22S)-3a,7a,22-trihydroxy] acid occurs in the bile of bony fish 11) whereas b-phocacholic [(23R)-3a,7a-23-trihydroxy] acid is present in the biliary bile acid of marine mammals, 12) ducks 13) and flamingos.14)The above findings of the species differences in the bile acid metabolism of vertebrates are, therefore, of interest from the viewpoint of their metabolism and physiological functions, as well as phylogenetic significance. For these reasons, new sites of "third" hydroxylation of CDCA are of considerable interest.As mentioned above, "third site" hydroxylation at C-1, -4, -5, -6, -12, -15, -16, -22 and -23 in CDCA has now been known and/or characterized in the literature. However, the occurrence of 14a-hydroxylated CDCA has not yet been reported, though it is a logical compound to be formed in vertebrates, as the 3a,5b,7a-trihydroxy compound having a tert-hydroxy group at C-5 does occur in some species. In a survey of the biliary bile acids of some 900 vertebrate species, unidentified C 24 trihydroxy bile acids were often present as major components. 15) Our labolatory has had a program aimed ...

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Dimethyldioxirane

Crandall

Curci²,

D’Accolti³

et al. 2005

Encyclopedia of Reagents for Organic Synthesis

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A highly efficient, stereoselective oxyfunctionalization of unactivated carbons in steroids with dimethyldioxirane†

Cited by 33 publications

References 22 publications

A comparative study of remote oxy-functionalization of unactivated carbons in 5β-steroids by dimethyldioxirane and 2,6-dichloropyridine N-oxide / ruthenium-porphyrin / HBr

A comparative study of remote oxy-functionalization of unactivated carbons in 5β-steroids by dimethyldioxirane and 2,6-dichloropyridine N-oxide / ruthenium-porphyrin / HBr

Synthesis of 3.ALPHA.,7.ALPHA.,14.ALPHA.-Trihydroxy-5.BETA.-cholan-24-oic Acid: A Potential Primary Bile Acid in Vertebrates

Dimethyldioxirane

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