The identification of Marker's lsquo;alpha;-ketodihydrolanosteryl acetatersquo; as 3beta;-acetoxylanost-9(11)-en-7-one

摘要

1972 581The Identification of Marker's ' a-Ketodihydrolanosteryl Acetate ' as3~-Acetoxylanost-9(1 I )-en-7-oneBy Lindsay H. Briggs,' J. P. Bartley, and P. S. Rutledge, Department of Chemistry, University of Auckland,Auckland, New ZealandIn addition to 3p-acetoxylanost-8-en-7-one (5) and 3~-acetoxylanost-8-ene-7,11 -dione (6). known products ofthe reaction, oxidation of 3p-acetoxylanost-8-ene (1 ) with chromic acid-acetic acid at 80" afforded 3p-acetoxy-lanost-9(1 l)-en-7-one (4). apparently identical with Marker's ' a-ketodihydrolanosteryi acetate '. Oxidation of3~-acetoxy-8a,9a-epoxylanostane (2) and 3~-acetoxylanosta-7,9(11 )-diene (3) under the same conditionsyielded the same three products.IN 1937, before the structure of lanosterol was estab-lished, Marker and his co-workers 1 oxidised 3p-acetoxy-lanost-8-ene (1) with chromic acid-acetic acid at 80"for 10 min and obtained ' a-ketodihydrolanosterylacetate,' C32H5203, m.p.150deg;, and ' p-ketodihydro-lanosteryl acetate,' m.p. 152". The P-isomer waslater identified by Barton and his co-workers2 as 3p-acetoxylanost-8-en-7-one (5). Repetition of the oxid-ation by later workers, however, has failed to yield thea-isomer .Oxidation of compound (1) under Marker's conditionshas now given three products, separated by columnchromatography on deactivated alumina. One wasidentified as the conjugated enone (ti), the second as thediketone (6), and the third, C32H5203, m.p. 150-152"'isomeric with the enone (5) is, in all probability, Marker's' a-ketodihydrolanosteryl acetate,' with structure (4).The compound does not absorb strongly in the U.V.above 220 nm, but i.r.bands at 1730 and 1700 cm-1indicate the presence of acetate and saturated carbonylgroups, respectively. The n.m.r. spectrum exhibitsa one-proton vinyl resonance at 6 5.43 and a one-protonsinglet at 6 2.32, values consistent with the presence ofa 9,ll-double bond. A weak negative Cotton effect,similar to that of p-acetoxylanostan-7-one (7), indicatesp-stereochemistry for the 8-proton. These facts supportthe identification as BP-acetoxylanost-9( 1 l)-en-7-oneMarker's ' a-ketodihydrolanosteryl acetate ' had amelting point (150") similar t o that of compound (4)(4).1 R. E. Marker, E. L. Wittle, and L. W. Mixon, J .Amev. 2 D. H. R. Barton, J. S. Fawsett, and B. R. Thomas, J .Chem. SOC., 1937, 59, 1368. Chem. SOL, 1951, 3147582 J.C.S. Perkin Iand underwent alkaline hydrolysis to ' p-ketodihydro-lanosterol ' (3p-hydroxylanost-8-en-7-one 2, ( 5 ; OH forOAc) , whose constitution was proved by acetylation to3~-acetoxylanost-8-en-7-one (5). Since alkaline hydro-lysis of the acetate (5) also afforded the same hydroxy-compound (5; OH for OAc), a simple isomerism of anunconjugated to a conjugated enone must have occurredduring the first hydrolysis. Our own product (4) wasalso isomerised to the conjugated enone (5; OH forOAc) by alkali. Although a direct comparison has notbeen made, the foregoing evidence indicates that Marker'sA solution of 3p-acetoxylanost-3-ene (2-0 g, 42 mmol)in acetic acid (60 ml) a t 80' was added rapidly to a solutionof chromium trioxide (1-08 g, 10.8 mmol) in acetic acid(90; 40 ml) and the mixture was maintained a t 80" for10 min.The cooled solution was poured into water(250 ml) and the precipitate was extracted with ether andworked up to yield a solid (2.1 g). This was chromato-graphed on deactivated alumina (120 g) .(i) Elution with light petroleum-benzene (4 : 1; 400 ml)gave a solid (0.35 g) which crystallised from chloroform-methanol as silky needles of 3P-acetoxyZanost-9( 1 l)-en-7-one(4) (0.3 g, 15), m.p. 150-152', a, +78' (c 0.86), 0.r.d.AcO cpoxidat i o 2' or-isomer ' has the structure (4). Barton and hisco-workers also obtained compound (a), but only as amixture with the enone (5).It was also transformedas above into the enone (5).33 p-Acetoxy-8a,9~~-epoxylanost ane (2) and 3 p-acet oxy-lanosta-7,9(11)-diene (3) are both oxidised underMarker's conditions to the same products (4)-(6).EXPERIMENTALU.V. spectra were determined for solutions in ethanolwith a Unicam SP 800A or Perkin-Elmer 137 spectro-photometer, i.r. spectra for solutions in chloroform with aPerkin-Elmer 237 spectrophotometer, n.m.r. spectra forsolutions in deuteriochloroform with a Varian A60 spectro-meter, with tetramethylsilane as internal reference, andoptical rotations for solutions in chloroform with a JascoORD-UV 5 spectrometer.Oxidation of 3P-A cetoxylanost-8-ene under Marker'sConditions.-3~-Acetoxylanost-8-ene, obtained as a by-product in the purification of lanosterol from ' isocholes-terol ' (purchased from van Schnappen and Soon, Veenen-daal, Holland) by Bloch's method,5 had S 0.68 (3H, s,18-H3), 1-00 (3H, s, 19-H,), 2.98 (3H, s, 3-OAc), and 4-42(lH, m, 3-H) p.p.m.3 D.H. R. Barton, P. J. L. Daniels, J. F. McGhie, and P. J.Palmer, J . Chem. SOC., 1963, 3675.4 I. G. Guest and B. A. Marples, J. Chem. SOC. (C), 1971,1468.~U,O + l38", 41330 +270deg;, +mi +222", ~,ocI +370deg;,and +I2,, +920', v- 1730 (acetate G O ) , 1700 (GO),and 1255 (GO) cm-l, 6 0-68 (3H, s, 18-H,), 1.12 (3H, s,19-H,), 2.05 (3H, s, 3-OAc), 4.51br (lH, 3-H), and 5.43br(lH, ll-H) p.p.m. (Found: C , 79-6; H, 10.7; 0, 10.0.Camp;,amp;3 requires C, 79.3; H, 10.8; 0, 9.9).(ii) Elution with light petroleum-benzene (7 : 3; 150 ml)gave a pale yellow solid which crystallised from chloro-form-methanol as needles (0.05 g), m.p.and mixed m.p.with 3P-acetoxylanost-8-en-7-one (5) 145-149' (lit.,3145--148"), 6 0.65 (3H, S, 18-H3), 1-20 (3H, s, 19-H3),2.02 (3H, s, 3-OAc), and 4-48br (lH, 3-H) p.p.m.(iii) Further elution with light petroleum-benzene(7 : 3; 900 ml) gave a yellow solid (0.9 g) shown by t.1.c.in benzene to be a mixture of compounds ( 5 ) , RF 0.11,and (6) RP 0-15.(iv) Further elution with light petroleum-benzene gavea yellow solid (0.1 g) which crystallised from chloroform-methanol in yellow plates, m.p. and mixed m.p. with3P-acetoxylanost-8-ene-7, ll-dione (6) 154-156" (lit.,s1.30 (3H, s, 19-H,), 2-01 (3H, s, 3-OAc), and 4-47 (lH, t ,J 7 Hz, 3-H) p.p.m.Isomerisation of 3p-Acetoxylanost-9( 1 l)-en-7-one (4) .-158-159'), S 0.79 (3H, S, 18-H3), 1.17 (3H, S, 32-H3),5 K.Bloch, F. Gautschi, and J. D. Johnston, J . Biol. Chem.,6 L. Ruzicka, E. Rey, and A. C . Muhr, Helv. Chim. Acta,1957, 224, 185.1944, 27, 4721972A solution of the acetoxy-enone (4) (1.5 g, 3-1 mmol) andpotassium hydroxide (0-5 g) in methanol (25 ml) washeated under reflux for 2-5 h. It was then poured intowater and the precipitate was extracted with ether. Work-up yielded a product which crystallised from ethyl acetate-methanol in needles of 3P-hydroxylanost-8-en-7-one (5 ;OH for OAc) (1.2 g, 80), identified by mixed m.p., i.r.,and n.m.r. spectra, and t.1.c.Oxidation of 3P-Acetoxy-8a,9u-e~oxyZanostane (2) and3P-Acetoxylanosta-7,9( 11)-diene (3) under Markerrsquo;s Con-ditions.-Solutions of the epoxide (2) * and the diene (3) *(50 mg, 0.1 mmol) were oxidised similarly. T.1.c. of theproducts in benzene showed that they contained the threeproducts (4)-(6).We thank the New Zealand Wool Research Organisationfor a Research Fellowship (to J. P. B.).1/1650 Received, 9th September, 1971