Site-selective hydroxylation of steroids via oxometalloporphinates covalently linked to ring D: introduction of hydroxyl groups into the C(9) and C(12) position of 5.alpha.-androstanes

Abstract

2957Brief illustrative experimental procedures serve to demonstrate the utility of these methods. First, treatment of 35 mmol of 5 with 50 mmol of LDA in 50 mL of THF for 2 h at 0 OC and hydrolytic workup gave a 96% yield of a 45:55 mixture of the cis and trans isomers of diphenyl-l-propenylamine (I 1). Although stoichiometric amounts of LDA are employed in this case, such isomerizations can be effected by catalytic amounts of LDA as well. Second, treatment of 20 mmol of 5 with 22 mmol of n-BuLi in 100 mL of THF at 0 OC for 1 h gave a deep red solution; then, 20 mmol of PhCHzCl were added and al-(6) A number of allylic diphenylamines, such as CH&H= CHCHPNPhl and PhC€h=CHCH2NPh2, have been prepared in thie manner. Eiech, J. J.; Chiu, C. S.; Shah, J. H. Unpublished studies.lowed to react for 6 h at 25 OC; hydrolytic workup and column chromatography of the dried and evaporated organic layer on silica gel (hexane:CHzClz = 8 2 as eluent) gave, separately, 4-phenylbutanal (75%) and recovered diphenylamine (95%). Third, treatment of 20 mmol of 5 with 22 mmol of n-BuLi in 100 mL of THF at 0 "C for 3 h and the subsequent addition of 20 mmol of benzophenone gave upon the usual hydrolytic workup a crude product that was recrystallized from ethanol to yield 65% of 2-(diphenylamino)-5,5-diphenyltetrahydrofuran, mp 124-125 OC. Treating this with dilute, aqueous HC1 eliminates diphenylamine and forms 2,2-diphenyl-2,3-dihydrofuran.Summary: Oxidation of synthetic manganese(II1) porphyrins attached to steroidal substrates at C(17) (cf. 2 and 3) gives rise to hydrogen atom abstraction at C(9) and/or C(12), thereby leading to hydroxyl incorporation at these sites. The use of more robust metalloporphyrins (cf. 9) results in substantial increases in the yields of hydroxylated 5cu-androstanes.

Two novel magnesium(II) meso-tetraphenylporphyrin-based coordination complexes: Syntheses, combined experimental and theoretical structures elucidation, spectroscopy, photophysical properties and antibacterial activity

“…3.1. Crystal structure description of (1) and (2) Crystallographic data and structural refinement details of (1) and (2) are shown in Table 1.…”

“…Macrocycles of meso-tetrakis [4-(benzoyloxy) were prepared as previously described [36][37]. Scheme S1 gives the main steps of the preparation of (1) and (2).…”

“…The design and synthesis of supramolecular coordination assemblies of porphyrin-based ligands complexes have received considerable attention due to their advantageous applications such as oxidation catalysts for hydroxylation of alkanes and epoxidation of alkenes [1][2][3][4], chemical sensors [5], and semi-conductors [6]… Several derivatives of porphyrin have been developed as photosensibilizating agents (PS) for photodynamic therapy (PDT) [7][8][9]. Recent in vitro studies demonstrated that porphyrins are also effective against viruses and yeasts [10,11].…”

Catalytic Oxidative Processes in Steroid Chemistry: Allylic Oxidation, β-Selective Epoxidation, Alcohol Oxidation and Remote Functionalization Reactions

“…"Meta"-substituted tetraphenylporphyrins attached to 5 -androstan-3 -ol derivatives have shown to lead to oxidation in the presence of PhIO [203]. Hydroxylations at either C(9) and/or C(12) of the steroid nucleus have been carried out by "ortho"-substituted porphyrins attached to the C(17) position of 5 -androstane [204]. The use of manganese(III) salen (N,N'-bis-(salicylideneamino)ethane) complexes attached to steroid substrates also mediated the hydroxylation of unactivated carbons with PhIO as the oxygen atom source [205].…”

An artificial cytochrome P450 that hydroxylates unactivated carbons with regio- and stereoselectivity and useful catalytic turnovers

“…Grieco and colleagues (18)(19)(20) have also shown that a metalloporphyrin can hydroxylate a steroid in an intramolecular reaction if it is covalently attached, but again, this is not a catalytic process with turnover. We have now made a catalyst that indeed binds a substrate, performs a hydroxylation catalyzed by a metalloporphyrin, and then releases the product to perform true turnover catalysis.…”