摘要:
SECTION C 0 rg a n ic C h e m i st ry Photo-oxygenation Studies of Some Derivatives of ent-Gibberellane t By M. F. Barnes, R. C. Durley, and J. MacMillan," Department of Organic Chemistry, The University, Bristol Attempts to photo-oxygenate the 2.3- and 16.1 7-double bonds in some derivatives of ent-gibberellane t were unsuccessful except in the case of allogibberic acid (VIII; 9a-H, R = H) and its methyl ester (VIII; 9a-H, R = Me), which reacted at the 16.17-double bond to give the expected 15-en-17-01s (IX; R = H) and (IX; R = Me), respectively. Acid-catalysed rearrangement of the latter (IX; R = Me) gave the hydroxymethyl derivative (X: R = Me) of methyl gibberate, which was identical with the methyl ester of the rearrangement product obtained from gibberellin A, 16.17-epoxide (XI; R = H).The major product from the rearrangement of the product of photo-oxygenation of methyl allogibberate was the 7 3 15-lactone (XIII) of 15-hydroxyallo- gibberic acid. IT has been suggested that gibberellin A, (I) may be the precursor of gibberellin A, (11; R1 = OH, R2 = H) in the seed of Phaseolus multijorus and that this conver- sion might occm in vivo by a process analogous to the sensitised photo-oxygenation of olefins to allylic hydro- peroxides. When this work was begun3 Nickon and Bagli4 had shown that such hydroperoxidation of steroidal olefins led stereospecifically to quasi-axial hydroperoxides by attack from the less hindered side. Thus, photo-oxygenation of gibberellin A, appeared to offer an attractive route to the sensitive ring A of gibberellin A,, since oxygen might be expected to attack from the p-face to give the 3-axial hydroperoxide (11; R1 = O,H, R2 = H) which could be reduced to gibberel- lin A, (11; R1 = OH, R2 = H).The gibberellin A, derivative (111) 1 was chosen for initial study to avoid the possible complicating reaction at the 16,17-double bond in gibberellin A, (I); but in the event this deriva- tive (111) was totally resistant to photo-oxygenation under conditions where ent-kaur-16-ene (IV; R = H) was photo-oxygenated in high yield.5 Since this result was obtained (1964) Nickon and his co-workers 6 have established that a pseudo-axial allylic hydrogen atom is required for photo-oxygenation by a process which they depicted as (V). It thus seemed probable that the failure of the derivative (111) to react was due to the unf avourable conformation imposed by the lactone bridge.Molecular models of the derivative (111) did t In agreement with Dr. J. W. Rowe (' The, Common and Systematic Nomenclature of Cyclic Diterpenes, 3rd revision, October 1968) we use the name gibberellane for the tetracyclic 12 indeed show that carbon atoms 1, 2, 3, 4, and 10 are coplanar and that both C(1)-H bonds are at an angle of 60" to the nodal plane of the 2,3-double bond. Recently Bachi and his co-workers have reported their failure to photo-oxygenate the decalin analogue (VI) of gibberellin A,. However the tetra-ol (VII) formed by removal of the lactone bridge in the gibberellin A, derivative (111), by reduction with lithium aluminium hydride, was also recovered unchanged under OUT conditions of photo- oxygenation.No explanation can be offered for this lack of reactivity; no cases of the photo-oxygenation of steroidal 2,3-enes have been reported. Neither double bond in gibberellin A, (11; R1 = OH, R2 = H) or its methyl ester (11; R1 = OH, R2 = Me) was photo-oxygenated. An interesting difference was observed between the 9-epimeric hydrolysis products (VIII; R = H) of gibberellin A,. In the case of epiallo- gibberic acid (VIII; 9@-H, R = H), with the same configuration as gibberellin A, at position 9, the 16,17- double bond was not photo-oxygenated, whereas allogib- beric acid (VIII; 9a-H, R = H) and its methyl ester were photo-oxygenated in moderate yield to give the allylic alcohols (IX; R = H or Me, respectively).These re- sults suggest that the configuration at position 9 influences the conformation of th, five-membered ring, and in terms of the process (V) suggest that the C(15)-aH bond is more nearly at right angles to the nodal plane of the 16,17-double bond in allogibberic acid (VIII ; 9cc-H, R = H) than in its 9p-epimer or in gibberellin A,. Thus 1 J. MacMillan, J. C. Seaton, and P. J. Suter, Tetrahedron, 2 For references and a review see G. 0. Schenk, Angem. Chem., 3 M. F. Barnes, Ph.D. Thesis, University of Bristol, 1965. 4 A. Nickon and J. F. Bagli, J . Amer. Chem. SOC., 1961, 83, 5 M. F. Barnes and J. MacMillan, J . Chem. SOC. (C), 1967, 1962, 18, 349. 1957, 69, 579. 1498. 1 .-I- 164. 6 A. Nickon and W. L. Mendelson, Caraud. J . Chem., 1965, 48, 1419; J .Org. Chem., 1965, 30, 2087; A. Nickon, N. Schwatz, J. B. DiGiorgio, and D. A. Widdowson, ibid., p. 1711. 7 M. D. Bachi, J. W. Epstein, Y . Herzberg-Minzly, and H. J. E. Loewenthal, J . Org. Chem., 1969, W, 126. ring system (i). named ent-gibberellane (ii) , with the same numbering. The basic ring system of the gibberellins is then1342 J. Chem. SOC. (C), 1970 has been suggested6 on the basis of the ease of 15,16- hydride shift on treatment with hydrochloric acid. Treatment of the allylic alcohol (IX; R = Me), from methyl allogibberate (VIII; 9a-H, R = Me), with 2 ~ - hydrochloric acid gave two crystalline products. One was the expected rearrangement product (X; R = Me), identical with the methyl ester of the acid obtained by treatment of gibberellin A, 16,17-epoxide (XI; R = H) with B~-hydrochloric acid at 100".This rational form- ation of the hydroxy-derivative (X; R = Me) of methyl gibberate provides further confirmation of the revised 8,9 structure for the rearrangement product 10 of gibberellin A, 16,Wepoxide (XI; R = H). In our hands, gib- berellin A, 16,17-epoxide, obtained as described by Keay and his co-workers,ll could not be obtained free from rearrangement products. It decomposed on silica during t.1.c.; indeed, the main product recovered from an attempt to purify the methyl ester (XI; R = Me) was the rearrangement product (XII; R = Me). The latter compound was identical with the methyl ester of the product (XII; R = H), obtained from the reaction of gibberellin A, 16,17-epoxide with water at 70-80" and the assignment of its structure was supported by the following spectroscopic data.The i.r. spectrum showed carbonyl absorption at 1713, 1730, and 1744 cm.-l, assigned respectively to ester, five-ring ketone, and lactone functions ; the mass spectrum contained an intense kf - 63 ion characteristic of the ring A structure of gibberellin A,; l2 and the n.m.r. spectrum contained two AB quartets, one of which (T 5.92 and 6.34, JAB 11 Hz) was assigned to the methylene protons of the hydr- oxymethyl group, and the other (7 6.25 and 6.8) showed JAB 7 Hz, typical for the 5,6-protons in a ring C/D re- arranged gibberellin.13J4 The n.m.r. spectrum of the methyl ester (XII; R = Me) was unusual for a gib- berellin derivative in that most of the proton signals could be precisely assigned (see Experimental section) with the aid of spin decoupling experiments.This spectroscopic evidence for the methyl ester (XII; R = Me) supports the revised structure (XII; R = H) for the rearrangement product of gibberellin A, 16,17-epoxide. The second, major product from the reaction of the photo-oxygenation product (IX; R = Me) with 2r;- hydrochloric acid was assigned structure (XIII) on the basis of the molecular formula, C18H,,0,, which corre- sponds to the loss of the elements of methanol, and the following spectroscopic evidence. The i.r. spectrum showed only one carbonyl absorption (1764 cm.-l), attributable to a y-lactone, and hydroxy-group absorp- 8 N. N. Gjrota and N. L. Wendler, Tetyahedyon Letters, 1966, 6431. 0 K. Schreiber, G. Schneider, and G.Sembdner, Tetrahedroiz, 1968, 24, 73. 10 K. Schreiber, G. Schneider, and G. Sembdner, Tetrahedron, 1966, 22, 1437. 11 P. J. Keay, J. S. Moffatt, and T. P. C. Mulholland, J . Chem. SOG., 1965, 6036. 12 R. Binks, J. MacMillan, and R. J. Pryce, Phytochemistvy, 1969, 8, 271. 13 T. MacMillan and R. T. Prvce. T . Chem. Soc. (C). 1967. 560. @ Me "zH Fc-'H I t p c /-17 Me & \\ H Me Me (IY) IY m1 (1x1 CHiOH L Me . .- (XI11 (XI111 (XIY) H a twist-envelope conformation is indicated for the five- membered ring in allogibberic acid (VIII ; 9a-H, R = H) by these photo-oxygenation results. A similar conform- ation for ring D in ed-kaurene-15a-01 (IV: R = OH) v \ J - 1 14 5. MacMjllan and R. 5. P&e; 1. Chem. SOC. (Cj; 1967; 740.Org. 1343 tion. The n.m.r.spectrum showed the absence of methoxycarbonyl protons but gave the signals T 2.9- 3.2 (3H, aromatic), 4.69 and 4-74 (each lH, =CH,), 558br (lH, s, lti-proton), 6.15 (lH, s, 6-proton), 6.60 (lH, distorted q, 9-proton), and 7.63 (3H, s, Me). The lactone (XIII) may be formed by a process similar to that represented in (XIV). Although no explanation can be offered for the lack of reactivity of the 2,3-double bond in the derivatives (111) and (VII) of gibberellin A,, or indeed of the analogue (VI) , towards sensitised pho to-oxygenation, the contrast- ing behaviour of the epimeric pair (VIII; 9p-H) and (VIII; 9a-H) suggests that photo-oxygenation may be a sensitive probe for allylic hydrogen stereochemistry in ring D of tetracyclic diterpenes. Further experiments on this point are in hand in the erct-kaur-16-ene and 13 p-kaur-16-ene series. EXPERIMENTAL M.p.s, determined with a Kofler hot-stage apparatus, were corrected. 1.r.spectra were obtained for Nujol mulls, unless otherwise stated, by use of a Unicam SP 200 spectro- meter. Optical rotations were obtained for solutions in acetone. N.m.r. spectra were determined at 100 MHz for solutions in deuteriochloroform with tetramethylsilane as internal standard. For column chromatography, silica gel (B.D.H. or Hopkin and Williams) was used. Kieselgel G plates (0.3 mm.) were used for analytical t.1.c. and Malinck- rodt Silica AR TLC-7G plates (0-9 mm.) were used for preparative t.1.c. ; t.1.c. plates were sprayed with 4% cerium(1v) sulphate in 7~-sulphuric acid. Mass spectra were obtained with an AEI MS9 instrument.Solutions were dried over sodium sulphate and evaporated with a Buchi rotatory evaporator. Light petroleum refers to the fraction, b.p. 60-80°. General Photo-oxygenation Procedure.-A solution of the olefin (100-750 mg.) and haematoporphorin (4-8 mg.) in pyridine (4-20 ml.) was irradiated in a vertical glass tube (id. 2 cm.) by two or four Phillips TLAW/33 fluorescent tubes, and oxygen was bubbled through the solution for 72 hr. The mixture was worked up by evaporation below 40". The residue in ethanol (40-70 ml.) was treated overnight with acetic acid (0.1-0.2 ml.) and potassium iodide (0.7- 5.0 g.). The brown solution, filtered from excess of potas- sium iodide, was evaporated; a solution of the residue in ethyl acetate was washed with aqueous sodium thiosulphate, then water, dried, and evaporated to give the crude product.Attempted Photo-oxygenations.-(a) The gibberellin A , deriv- ative (111). The lactone (750 mg.) and haematoporphorin (6 mg.) were irradiated in pyridine (15 ml.) in a stream of oxygen for 77 hr. The crude product, a brown solid, was shown by t.1.c. to contain only starting material, and was purified by column chromatography on silica gel. Elution with benzene-ethyl acetate (1 : 4), followed by crystallis- ation from acetone-light petroleum gave the starting lactone (111) as needles (690 mg.), m.p. and mixed m.p. 153-154", identified also by its i.r. spectrum. (b) The tetra-ol (VII). The tetra-ol (100 mg.) and haematoporphorin (4 mg.) were photo-oxygenated for 72 hr.The crude product showed only one spot, corresponding to starting material ct.1.c. on silica gel with ethyl acetate- methanol (19 : l)]. Purified by preparative t.1.c. with the same solvent it was crystallised from acetone-light petro- leum to give unchanged tetra-ol (VII) as prisms (65 mg.), m.p. 142-152', identified by mixed m.p. and i.r. spectrum. (c) Under similar conditions the following compounds were recovered unchanged and in high yield : gibberellin A, (11; R1 = OH, Ra = H), gibberellin A, methyl ester (11; R1 = OH, Ra = Me), and epiallogibberic acid (VIII; 9P-H, R = H). In each case the crude product showed only starting material on t.l.c., and there was no indication of hydroperoxide formation on treatment with acetic acid and potassium iodide. Preparation of the Tetra-ol (VII).-The lactone (111) (150 mg.) in tetrahydrofuran (15 ml.) was added dropwise to a stirred suspension of lithium aluminium hydride (300 mg.) in boiling tetrahydrofuran. Heating was then continued for 48 hr.To the cooled solution was added ethanol-ether, then saturated ammonium chloride. After removal of the volatile solvents in vacuo at 20°, water was added, and the resulting emulsion was extracted with ethyl acetate (5 x 10 ml.). The product, a gum (140 mg.), was purified by pre- parative t.1.c. with ethyl acetate-methanol (19 : 1) as sol- vent. Elution of the main spot and recrystallisation from acetone-light petroleum gave the tetra-ol (VII) as needles, m.p. 141-154' (Found: C, 70.7; H, 9.3. C1,H,,O, re- quires C, 70-8; H, 9.4%), vm, 3450br (OH) and 1060 (C-0) cm.-l (no C=O absorption).Photo-oxygenation of Allogibbevic Acid (VIII ; 9a-H, R = H).-Anhydrous allogibberic acid (480 mg.) and haematoporphorin (9 mg.) in pyridine (20 ml.) were irradi- ated for 72 hr. in a stream of oxygen. The crude product was methylated with diazomethane, then chromatographed on a column (6 x 1 cm.) of silica gel. Elution with benzene (2 1.) gave methyl allogibberate (247 mg.), m.p. and mixed m.p. 97-99' ; further elution with benzene-ethyl acetate (4 : 1) gave the allylic alcohol (IX; R = Me), which crystallised from ethyl acetate-light petroleum in needles (110 mg.), m.p. 161-163" (Found: C, 72.5; H, 7.1%; M+, 314. C,,H,,O, requires C, 72.6; H, 7.1%; M , 314), vmx. 3370br, 1718, 1650, 1598, 1275, 1190, 1115, 1020, 982, 890, 831, and 798 cm.-l.The allylic alcohol (IX; R = Me) (123 mg.) was also obtained directly by photo-oxygenation of methyl allogib- berate (500 mg.) and haemotoporphorin (8 mg.) in pyridine (20 ml.). Gibberellin A , 16,17-Epoxide (XI ; R = H) .--Gibberellin A, was epoxidised as described by Keay and his co-workers.ll The product had m.p. 234-238", v,, 3495, 2600, 1759, 1730, 1719, and 1635 cm.-l. T.1.c. on silica gel in ethyl acetate-chloroform-acetic acid (15 : 5 : 2) gave three spots; decomposition probably occurs under these conditions, as in the case of the methyl ester (see later). Rearrangement of Gibberellin A , 16,17-Epoxide (XI; R = H) ; Preparation of the Hydroxymethyl Ketone (XII; R = H).-(a) With water. The epoxide (90 mg.), in water (20 ml.), was heated a t 70-80" until complete dissolution had occurred.When ihe solution was cooled to 0" the hydr- oxymethyl ketone (XII; R = H) separated as needles, m.p. 242-4244', vmax. 3505, 2790, 1744sh, 1730, 1713, and 1632 cm.-l. The methyl ester (XII; R = Me), prepared with diazomethane, crystallised from acetone-light petroleum in needles, m.p. 218-220", M+, 376, v,, 3590, 3500, 1748sh, 1732, 1722, and 1630 cin.-l, T ([2H,]pyridine) 3.60 (d, J 9 Hz, H-l), 3-93 (q, J 4 and 9 Hz, H-2), 5.32 (d, J 4 Hz, H-3),J. Chem. SOC. (C), 1970 6.25 (d, J 7 Hz, H-5), 6.8 (d, J 7 Hz, H-6), 6.93 (d, J 4 Hz, H-9), 7.37 (d, J 12 Hz, H-llb), 8.10 (m, H - l l ~ ) , 8.47 (d, J 4 Hz, H-120: and p), 8.49 (s, H-140: and p), 7-45 and 7.73 (4, JAB 10 Hz, H-15cr and p), 5.92 and 6.34 (9, JAB 11 Hz, CH,*OH), 6-44 (s, OMe}, and 8.39 (s, CMe).(b) By t.1.c. The epoxide was esterified with diazo- methane and the crude product was subjected to prepara- tive t.1.c. on silica gel in ethyl acetate-benzene ( 9 : 1). Elution of the main spot with ethyl acetate, and recovery, gave the methyl ester (XII; R = Me), identical (m.p., t.l.c., and mass, ir., and n.m.r. spectra) with the compound obtained in (a). Rearrangemefit of Gibberellin A, 16,17-Epoxide (XI; R = H) with SN-Hydrochlovic Acid : Preparation of the Hydroxy- methyl Ketone (X; R = H).-The epoxide (40 mg.) in 2~-hydrochloric acid (20 ml.) was refluxed for 1.5 hr. When the solution was cooled, the hydroxy-derivative (X; R = H) of gibberic acid separated as small plates (25 mg.), m.p. 282--284", v,, 3470, 2640, 1741, 1710, and 1599 cm.-l.The methyl ester (X; R = Me), prepared with diazo- methane, crystallised from ether-light petroleum as plates, m.p. 157-159' (Found: M f , 314.1510. C,,H,,O, requires M , 314*1518), vmx. 3490, 1733, 1720, and 1601 crn.-l. Rearrangement of the Allylit Alcohol (IX; R = Me).-A solution of the allylic alcohol (30 mg.) in 2~-hydrochloric acid ( 5 ml.) was boiled for 1.5 hr. Extraction of the cooled solution with ethyl acetate gave a gum (21 mg.) which showed three strong bands, RF 0.35, 0.50, and 0.68 @repara- tive t.1.c. on silica gel in benzene-ethyl acetate (7 : 3)]. These bands were extracted with ethyl acetate to yield three compounds: (a) an intractable oil (2.5 mg.) (RF 0.68) ; (a) a product (5 mg.) (Rp 0.36) which was crystallised twice from ether-light petroleum to give prisms (3 mg.), m.p. 156-158', identical (mixed m.p., t.l.c., and i.r. and mass spectra) with the methyl ester (X; R = Me) obtained by rearrangement of gibberellin A, 16,17-epoxide with 2rv- hydrochloric acid; and (c) a product (10 mg.) (RF 0.50) which was crystallised twice from ether-light petroleum to give the lactone (XIII) as needles (7 mg.), m.p. 162-165' (Found: Mf, 282.1259. C1,Hl8O, requires M , 282.1256), v , ~ ~ . 3450, 1755, 1675, and 1600 cin-l, v,,, (CHCI,) 3630, 3450br, 1764, 1675, and 1600 cm.-l, T 2.9- 3.2 (3H, aromatic, 4-69 and 4.74 (=CH,), 5.58br (s, )CH-0), 6.15 (s, ArCHCO), 6-60 (4, ArCH<), and 7.63 (s, ArCH,) [0/012 Received, Jafiwa~y 5th, 19701
ISSN:0022-4952
DOI:10.1039/J39700001341
出版商:RSC
年代:1970
数据来源: RSC