Straightforward synthesis of 2,2,4,4,5,7,7-d7-cholestane: a new deuterated standard in petroleum analysis

Abstract

Recebido em 15/1/13; aceito em 18/4/13; publicado na web em 17/7/13 A short and efficient synthesis of heptadeuterated 2,2,4,4,5,7,7-d7-cholestane (1) from cholesterol (3) is described. The deuterated material will be useful for the analysis of different sources of petroleum in analytical geochemistry laboratories as internal standard for quantification of steranes via gas chromatography-mass spectrometry (GC-MS).Keywords: total synthesis; steroids; deuterated standard. INTRODUCTIONThe identification of organic structures in the environment can be very complex 1 with various processes frequently acting to modify structures and/or distributions of key compounds used as biomarkers. In some situations, examination of the relative distributions of biomarkers can be used as a method of fingerprinting and can be sufficient in providing the necessary answers. Unfortunately, this is frequently not the case, notably for the trace concentrations common in very mature petroleum samples. 2 Other examples include the recognition of mixed oil-sources with very similar biomarker profiles, found both in exploration and oil-spill studies, 3 and the correct interpretation of the changes in organic composition resulting from laboratory simulation experiments with geological materials by heating to understand petroleum generation, transformation or migration. 4 In such cases, absolute quantification can be mandatory and availability of a standard of the compound of interest or a structurally related analog is essential. Unfortunately, the necessary standard is frequently not available, notably for complex structures. This problem is aggravated by the fact that, even when commercially available, such standards are extremely expensive for routine use, some easily costing over a thousand dollars for quantities in the milligram range.The main objective of this work was to develop a simple synthetic scheme to prepare deuterated cholestanes (Scheme 1), frequently used as standards for quantification of steranes, biomarkers of great interest in petroleum and petroleum-related samples, in high yield and purity, using readily available reagents and starting materials. The synthesis should be simple enough to be performed by chemists with basic synthetic training in order to be useful, as an alternative, to the purchase of expensive commercial standards. RESULTS AND DISCUSSIONOur synthetic route (Scheme 2) starts with the oxidation of cholesterol (3). We employed an excess of PCC (7.0 eq.) in a dichloromethane suspension in the presence of cholesterol (3) to simultaneously promote two chemoselective, oxidation reactions, to furnish the product 4-cholesten-3,6-dienone (4) at a yield of 83%. Compound (4) was then submitted to catalytic hydrogenation conditions 5 at 70 psi of H 2 with 10% Pd-C and ethyl acetate as solvent for 40 hours in a Parr Apparatus, giving the corresponding 3,6-cholestandione (5) in quantitative yield.Various procedures described in the literature to introduce deuterium atoms at the alpha positions to the carbonyl functio...

H-Atom Abstraction vs Addition: Accounting for the Diverse Product Distribution in the Autoxidation of Cholesterol and Its Esters

“…Briefly, the 3-OH of pregnenolone was silylated with TIPS-Cl and the product deuterated based on the method of de Miranda et al, resulting in the quantitative formation of 5 . Although attempts to couple 5 and 1-bromo-4-methylpentane by Wittig chemistry resulted in partial D/H exchange, the analogous Grignard reaction proceeded without loss of D. The subsequent elimination resulted in a mixture of three alkenes (purported to be 55% Δ 20(22) , 25% Δ 20(21) , and 20% Δ 17(20) when carried out on a similar substrate) .…”

Synthesis of Deuterium-Labeled Steroid 3,6-Diols

“…For the obtaining of compounds with deuterium atoms in other positions we used the reaction of proton-deuterium exchange in the -positions to the carbonyl functions. It is known that D 2 O in the presence of NaOD in different solvents was used to replace acidic hydrogens to deuterium atoms in -positions to carbonyls of steroids [10,11]. We added a D 2 O with a small amount of Et 3 N for alkaline condition to a solution of cholest-4-ene-3,6-dione (2) in AcCN.…”