No. 10 4049

Chem. Pharm. Bull. 35(10)4049-4055(1987)

Absolute Configurations of Chaetochromin A and Related

Bis(naphtho-ƒÁ-pyrone) Mold Metabolites

KIYOTAKA KOYAMA,*, a SHINSAKU NATORI,a and YOICHI IITAKAb

Meiji College of Pharmacy,a Yato-cho, Tanashi-shi, Tokyo 188, Japanand Faculty of Pharmaceutical Sciences, University of Tokyo,b

Hongo, Bunkyo-ku, Tokyo 113, Japan

(Received April 1, 1987)

The absolute configuration of chaetochromin A (1) was established by X-ray analysis of the 6-Ο-p-bromobenzoate (15) of the 5,5',6',8,8'-ventamethvl ether (14). The stereochemistry of the 9-9'

bond was proved to be S. in agreement with the result obtained by the application of the exciton chirality method. From the circular dichroism spectra, the absolute configurations of chaetochro-mins B, C and D (2-4) and cephalochromin (8) were proved to be S, while those of ustilaginoidins A, B, and C (5-7) were R. The stereochemistry of other bis(naphtho-y-pyrones) is discussed.

Keywords Chaetochromin; cephalochromin; ustilaginoidin; bis(naphtho-ƒÁ-pyrone); myco-

toxin; CD; X-ray analysis; absolute configuration; exciton chirality

Chaetochromin A (1) is a mycotoxin, first isolated from Chaetomium virescens

UDAGAWA (C. thielavioideum CHEN),1) and exhibits toxicity to experimental animals2) and

antitumor activities.3) The structure and the relative stereochemistry were established by the

previous studies") and three related compounds (2-4) were also isolated from C. gracile

UDAGAWA,4) but the absolute configurations (including the atropisomerism) have not been

established.

As related bis(naphtho-ƒÁ-pyrone) mold metabolites, ustilaginoidins A, B, and C (5-7)

from Claviceps virens (anamorph state: Ustilaginoidea virens (COOKE) TAKAHASHI),5)

cephalochromin (8) from Cephalosporium sp.,6) Verticillium sp.,7) and Nectoria spp.,8) and

isoustilaginoidin A (9) (the antipode of 5) and dihydroisoustilaginoidin A (10) from

Verticillium sp.7) are known. Among these compounds, the absolute configurations of

ustilaginoidins (5-7) were proposed to be R based on the positive Cotton effect at around

400 nm in the optical rotatory dispersion (ORD) compared to those of biaryls,9) but the

application of the results to the absolute configuration of nigerone (11) from Aspergillus

niger10) was contradictory, and an unambiguous assignment of the stereochemistry of these

compounds was required.10) The circular dichroism (CD) data for 8-107) and the ORD data

for aurasperone A (12) from A. niger11) were given but the absolute configurations were not

discussed in the above papers.

Recently we have recognized the antitumor- activities of chaetochromins and related

compounds,12) and the establishment of the absolute configurations of these compounds was

required to confirm the structure-activity relationship of bis(naphtho-y-pyrone) derivatives.

In order to determine the absolute configuration of chaetochromin A, the ƒ­-p-

bromobenzoate (15) of chaetochromin A pentamethyl ether (14) was prepared from its

tetramethyl ether4) (13). Dark-yellow thick plate crystals of (15) were grown in hexane-ethyl

acetate solution and a small crystal with approximate dimensions of 0.15 •~ 0.3 •~ 0.45 mm was

used for the X-ray diffraction study. The crystal was mounted on a Philips PW1100

diffractometer and the lattice parameters and intensity data were measured with the use of

4050 Vol. 35 (1987)

graphite-monochromated CuIC radiation. The crystal data are: 6-O-p-bromobenzoyl-chaetochromin A 5,5 ',6',8,8 '-pentamethyl ether, C4 H39011 Br, Mr 799.7; orthorhombic, space group P212121, Z=4, Dcal = 1.377 g cm '; lattice constans, a= 14.642(8), b = 24.147(12),

c= 10.908(6) A, U= 3857 A3; p for Cuk, ----- 19.5 cm' .

Chart 1

No. 10 4051

(a) (b)

Intensities of 5229 reflections in the 20 range of 6 ° through 156 ° were measured as above the 2a(I) level, including 835 Friedel pairs and 93 symmetry equivalent reflections. The number of possible reflections in the same angular range was 4580. The difference of the intensities of Friedel pairs was estimated as R(F) = Eli F(hkl) I I F(EkT) I I II F(hkl) I, where the sum was taken for 835 pairs, giving an R(F) value of 0.061.

The crystal structure was determined by the heavy atom method and the atomic

parameters were refined by the block-diagonal-matrix least-squares calculation. Hydrogen atoms were not included since most of the hydrogen atoms are methyl hydrogens and it was not possible to locate many of them on the difference electron-density map due probably to the rotational oscillation of methyl groups. Anisotropic refinement gave an R value of 0.074 for 4301 reflections.")

Absolute structure was determined by the anomalous dispersion method. Dispersion correction terms for C, 0 and Br scattering factors for CuKc, radiation were taken from International Tables for X-Ray Crystallography (1972). The observed and calculated structure factor ratios robs and roa, were compared for the Friedel pairs, where robs = IF obs(hk1) Ill F obs(fikT) 1, a, b* and c* axes were taken in the right-handed system and r cal=

I Fcal (hkl) F ET) 1; Foal's were calculated with the refined atomic parameters and anom-alous dispersion corrections for C, 0 and Br. Of the total of 279 Friedel pairs for which both

robs and real differ by more than 3% from unity and the difference in observed structure factors,

II F obs(hk1)I F obs(hk1)II is estimated to be greater than 2o[F(hk1)], 244 pairs showed consistently the absolute configuration given in Fig. 1.

Subsequent least-squares refinement allowing the dispersion corrections gave R values of 0.070 and 0.076, the latter being for the inverted structure.

The corresponding bond lengths and angles for the two naphtho-y-pyrone moieties are in

good overall agreement with each other and are close to those expected for the chemical structure. The differences between two skeletons are almost within the limits of experimental error. The largest differences are found in C3—C12 = 0.067 A and C7-C6—05A = 3.4 °. The conformations of the two skeletons are also not very different. The puckering of the y-pyrone

Fig. 1. The Molecular Structure of 6-O-p-Bromobenzoylchaetochromin A 5,5',6',8,8'-Pentamethyl Ether (15) Showing the Absolute Configuration

The figures were drawn by PLUTO. (a) Viewed down to the mean molecular plane . (b) Viewed along the C9-C9' bond.

4052 Vol. 35 (1987)

ring may be characterized by the torsional angles, C4A-C10A-01-C2 and C4A-C4-C3--C2 . They are 32.3(9) and -26.6(8) respectively for the unprimed ring and 37 .9(9) andｰ17 .8(8) respectively for the primed ring. Although the bond C4A -C 10A has a partial

double bond character, C4A--C4 and ClOA 01 are twisted due to the puckering . The torsion angles, C4-C4A-C10A-01 and C4'---C41A CIO/A-01' are - 3.8(9) and -11:5(9) , re-spectively, for the two y-pyrone rings. To illustrate the distortion of the naphtho-y-pyrone moiety, the least-squares plane through the naphthyl skeleton atoms has been calculated and the deviations of atoms from the plane are listed in Table I.

The configurations at the 2-, 2'-, 3- and 3'-positions were proved to be R, R, R, and R, respectively. The relative configuration of the 2,3-dimethyl group was shown to be trans by

proton and carbon-13 nuclear magnetic resonance ('H- and '3C-NMR) analyses. The torsion angles shown in Table II gave support to the NMR assignments."'

The two planes (formed by the unprimed and primed atoms, respectively) make an angle of 65.7 which can be compared to 45 in the gas-phase biphenyl molecule ,'`' 76.6 in ( )- 2,2'-dihydroxy-1,1'-binaphthalene-3,3'-dicarboxylic acid dimethyl ester,' 5' 58 in 1,4,5,8- tetraphenylnaphthalene,16) 77.6 in binaphthylbis(18-crown-6)17) and 78.7 in 3,3'-(1 ,1'-bi-2- naphthol)-21-crown-5.18' The aryl---aryl bond length, C9-C9' of 1.487(10) A is also in good agreement with those in the above-mentioned compounds: 1.48 A,'4) 1.49(3) A,15

1.504(4) A,'') 1.465(7) A' 7) and 1.491(4), A,' 8) respectively. The torsion angles about the bond connecting the two naphthyl groups, C9A-C9-C9'---C91A and C8 C9-C9' C8' are 72.2(8) and 65.1(8) , respectively. The sign of the angle indicates the absolute configuration of the

TABLE I. The Least-Squares Plane through the Naphthol Skeleton Atoms

and the Deviations of Atoms from the Plane

TABLE II. Torsional Angles ( ) of the ;i-Pyrone Part of 6-0-p-Bromobenzoyl-

chaetochromin 5,5',6',8,8'-Pentamethyl Ether (15)

No. 10 4053

atropisomer and it is proved to be S.

It is well known that the CD Cotton effects due to chiral exciton coupling between two or

more chromophores suggest the absolute stereochemistry in a nonempirical manner.19) The

application of the method to binaphthyl chromophores has been published.2°'2" The

observed dihedral angle (65.7 °) of the two aromatic moieties guarantees the applicability of

the method.'"

The CD curves of chaetochromin A (1)) exhibit strong positive first ([0] 50 x 104

(294 nm)) and second negative ([0] - 43 x•@104 (266 nm)) Cotton effects due to the couplings

between the 1Bb transitions of the two naphthalene chromophores and this shows that the two

long axes are twisted in a clockwise manner. This conclusion is in accord with the result

established by X-ray analysis. Since the CD spectra of chaetochromins A-D (1-4) are

superimposable, all these naphtho-y-pyrones from Chaetomium spp. have S-configurations of

the 9-9' bond.

Cephalochromin (8) has been isolated from several fungal sources.") As described in

Experimental, the compound was obtained from Acremonium butyri (syn. Nectoria virides-

cens8)) in this work. As shown in Fig. 2, the compound shows strong positive first ([0] 51 x 104

(294 nm)) and negative second ([0] - 49 x 104 (266 nm)) Cotton effects, indicating the same S-

configuration as chaetochromins. It was reported that the treatment of cephalochromin (8)

with iodine in acetic acid gave ustilaginoidin A (5),6) but the product must be isoustilaginoidin

A (9) (vide infra) or the racemate of 5.

The structures (5-7) of ustilaginoidins A, B, and C, red coloring matters obtained from

the smutted balls formed by the infection of Claviceps virens (anamorph state: Ustilaginoidea

virens) on the spikes of rice plant, were firmly established by chemical, spectroscopic, and

synthetic methods.5) Empirical application of the ORD behavior of biaryls to the absolute

configurations was done and the observed positive Cotton effect at the higher wavelength

region (around 400 nm) suggested the R-configuration. We tried to isolate the pigments.22)

The CD spectrum measured for a sample of ustilaginoidin A showed negative first (I-01

-46×104 (290 nm)) and positive second ([01 31 x 104 (261 nm)) Cotton effects (Fig. 2). Thisand the reported data') showed that the two long axes of the naphthalene chromophores in ustilaginoidins A, B, and C (5 7) are twisted in a counter-clockwise manner, contrary to that in chaetochromins (1-4) and cephalochromin (8), and indicate R-configuration of the compounds. The antipode of ustilaginoidin A named isoustilaginoidin (9), the dihydro compound (dihydroisoustilaginoidin A) (10), and the tetrahydro compound (identical with cephalo-

Fig. 2. CD Spectra of Chaetochromin A, Cephalochromin, and Ustilaginoidin A (in Dioxane)

4054 Vol. 35 (1987)

chromin) (8) were isolated from Verticillium sp.') The reported CD data of these compounds')

clearly indicated strong split bands around 280 nm with first positive and second negative

signs, which suggest S-configuration.

From these facts it is clear that the stereochemistry of the binaphthyl moiety of the 9,9'-

binaphtho-y-pyrones is the same in the compounds from Chaetomium sp. (1-4), Verticillium

sp. (8 10), and Cephalosporium sp. (8) but is antipodal in those from Ustilaginoidea (5-7) .

Nigerone (11) is a 10,10'-bisnaphtho-y-pyrone from Aspergillus niger.1°) The compound

shows negative ORD and CD Cotton effects in the long wavelength region (about 430 nm) ,

opposite to ustilaginoidins, and strong negative first and positive second effects in the short

wavelength region (around 280 nm), similar to•@ ustilaginoidins.101 The latter observations

clearly indicated the negative chirality of the chromophores, suggesting R-configuration .

Aurasperone A (12) is a 10,7'-bisnaphtho-y-pyrone from A. niger.") The ORD curve ,

showing a clear Davydov splitting, was recorded for the compound though the stereochem-

istry was not discussed.") The curve clearly indicates positive first and negative second effects ,

indicating positive chirality of the chromophores and suggesting S-configuration of the

compound.

Racemization involving binaphthyl bonds subject to restricted rotation has been

reported for the binaphthopyrones.5'1°' in In the case of cephalochromin (8) and chaetoch-

romin A (1) with chiral carbons in the y-pyran ring, epimerization of the methyl groups occurs

simultaneously. Examination of the racemization of the binaphthyl bond and characteri-

zation of the products are in progress.

Experimental

All melting points were determined on a Yanagimoto micromelting point apparatus and are uncorrected. The

11-1- and 13C-NMk spectra were recorded on a JEOL GX -400 CH 400 MHz and 13C 100 MHz) spectrometer in

CDC13 with tetramethylsilane as an internal standard. Chemical shifts are recorded in ppm (6). Mass spectra (MS)

were taken on a JEOL JMS-D300. Ultraviolet (UV) and infrared (IR) spectra were measured with a Shimadzu UV-

240 spectrophotometer and a JASCO A-102 infrared spectrophotometer. The [a],, values were measured with a

JASCO DIP-140 digital polarimeter.

Kiesel gel 60F254 (Merck) precoated plates were used for thin-layer chromatography (TLC) and the spots were

detected by UV illumination. Column chromatography was carried out on 70-230 mesh silica gel (Merck). High

performance liquid chromatography (HPLC) was carried out by using a Waters M45J pump with an Oyo-Bunko

Uvilog-5 IIIA UV detector.

Chaetochromin A 5,5',6,8,8'-Pentamethyl Ether (14) A CH2C12 solution of chaetochromin A 5,5',8,8'-

tetramethylether4) (13) (28.4 mg) was methylated with ethereal CH2N2 at room temperature for 2 h and the reaction

mixture was purified by HPLC (Nucleosil 50-5) with hexane-EtOAc (1 : 1) to give 14 (8.3 mg), yellow leaflets (from

Me0H-H20), mp 154-160 °C, [a]p + 386 ° (c= 0.09, dioxane). MS m/z: 616.2310 (M+, Calcd for C35H36010:

616.2308). UV 4,;:,:ane nm (1): 231 (47700), 259 (47700), 290 (77500), 330 (11000), 341 (9300), 391 (8600). IR

v ,1,111x. cm -1: 3350, 1690, 1625, 1613, 1560, 1370, 1355, 1330, 1280, 1130, 1065. CD (dioxane) [O]2° (nm): - 476500 (253),

- 40800 (272), 0 (276), + 925700 (290),•@ 0 (321), - 68100 (342), 0 (360), +8200 (400). 1H-NMR (CDC13) 6 : 1.17, 1.19

(3H x 2, each d, J=6.7, 7.0, 3,3'-CH3), 1.38, 1.39 (3H x 2, each d, J=6.1, 5.8, 2,2'-CH3), 2.51, 2.51 (1H x 2, each dq,

J=11.0, 6.7; 11.0, 7.0, 3,3'-H), 3.76, 3.79 (3H x 2, each s, 8,8'-OCH3), 4.00 (3H, s, 6'-OCH3), 4.07, 4.14 (3H x 2, each

s, 5,5'-OCH3), 4.11, 4.13 (1H x 2, each dq, J=11.0, 6.1; 11.0, 5.8, 2,2'-H), 6.63, 6.69 (1H x 2, each s, 7,7'-H), 6.32,

6.32 (1H x 2, each s, 10,10'-H), 10.18 (1H, s, 6-0H). 13C-NMR (CDC13) 6 : 10.47, 10.59 (3,3'-CH3), 19.63, 19.75 (2,2'-

CH3), 48.32, 48.48 (3,3'-C), 56.12, 56.27, 56.37 (6',8,8'-OCH3), 62.91, 64.32 (5,5'-OCH3), 77.54, 77.59 (2,2'-C), 93.75,

97.05 (7,7'-C), 105.15, 105.69 (10,10'-C), 108.51, 109.03, 109.30, 109.58, 112.23, 112.57 (4a,4'a,5a,5'a,9,9'-C), 139.71,

140.70 (9a,9'a-C), 156.84, 157.34 (10a,10'a-C), 158.35, 158.35 (8,8'-C), 159.68, 160.22, 160.30, 161.29 (5,5',6,6'-C),

192.92, 193.10 (4,4'-C).

6-O-p-Bromobenzoylchaetochromin A 5,5',6',8,8'-Pentamethyl Ether (15) A solution of 14 (24.7 mg) and p-

bromobenzoyl chloride (25 mg) in pyridine (3.5 ml) was stirred gently under N2 in the dark for 2 h. After filtration, the

reaction mixture was evaporated to dryness. The residue was chromatographed over silica gel using benzene-EtOAc

(10 : 1) as the developing solvent. Purification by HPLC (Develosil 60-3) with benzene-EtOAc (8 : 1) gave 15

(10.5 mg), dark yellow prisms (from hexane-EtOAc), mp 285-290 °C, [a]p + 262 ° (c = 0.077, dioxane). MS m/z: 798

(M t), 616. UV /1`,1,;:',:a" nm (1): 235 (61600), 250 (71700), 273 (69900), 284 (89300), 325 (14800), 339 (12900), 381

(9800). IR v mBX cm-1: 1740, 1692, 1615, 1590, 1567, 1345, 1270, 1260, 1125, 1097, 1010, 750. CD (dioxane) [0]20 (nm):

No. 10 4055

-459600(255) , - 271600 (266), 0 (274), +1211600 (285), 0 (315), - 91900 (337), 0 (363), +14600 (394). 1H-NMR (CDCl3) ƒÂ : 1.14, 1.18 (3H •~ 2, each d, J=6.7, 7.0, 3-, 3'-CH3), 1.38, 1.39 (3H •~ 2, each d, J=5.8, 5.8, 2,2/-CH3), 2.50,

2.52 (1H •~ 2, each dq, J=11.0, 6.7; 10.7, 7.0, 3-, 3'-H), 3.79, 3.79, 3.80, 4.09 (3H x 4, each s, 5,5',8,8'-OCH3), 4.01

(3H, s, 6-OCH3), 4.11, 4.12 (1H •~ 2, each dq, J=11.0, 5.8; 10.7, 5.8, 2,2'-H), 6.32, 6.44 (1H •~ 2, each s, 10,10'-H),

6.64, 7.03 (1H •~ 2, each s, 7,7'-H), 7.71 (2H, d, J=8.5, 23, 25-H), 8.19 (2H, d, J=8 .5, 22, 26-H). 13C-NMR (CDCl3)

6: 10.54, 10.56 (3,3'-CH3), 19.73, 19.81 (2,2'-CH3), 48.55, 48.55 (3,3'-C), 56.25, 56.35, 56.46 (6',8,8'-OCH3), 63.02,

63.71 (5,5'-OCH3), 77.68, 77.71 (2,2'-C), 93.50, 107.07 (7,7'-C), 105.09, 105.87 (10,10'-C), 109.02, 112 .37, 112.47,

112.54, 113.60, 115.94 (4a,4'a,5a,5'a,9,9'-C), 128.54, 128.75 (21,24-C), 131.83, 131.95 (22,23,25,26-C), 140.30, 140.32

(9a,9'a-C), 157.43, 157.46, 157.56, 158.15 (8,8',10a,10'a-C), 149.40 (6-C), 159.61, 160.60, 161.39 (5,5',6,6'-C), 164.74

(17-C), 193.19, 193.29 (4,4'-C).

Isolation of Cephalochromin (8) from Acremonium butyri The strain (CBS 479.69) was incubated in stationary

culture on sterilized wheat (110 g) at 26 °C for 30 d. The moldy wheat was extracted three times with EtOAc (200 ml)

for 24 h at room temperature. The extract was chromatographed over silica gel (treated with 3% oxalic acid) using

CH2Cl2 as the developing solvent, and purification by HPLC (Nucleosil 50-5, treated with 3% oxalic acid) using

hexane-EtOAc (4 : 1) as the developing solvent gave 8 (120 mg), yellow powder (from CH2Cl2-hexane), mp 214-

215 •Ž. MS m/z: 518.1224 (M+, Calcd for C281422010: 518.1213). UV ƒÉdioxanemax nm (ƒÃ): 210 (52100), 232 (60200), 269

(53100), 292 (61200), 325 (15800), 338 (10200), 413 (10200). IR vKBrmax cm -1: 3400, 1640, 1630, 1588, 1445, 1383, 1365,

1340, 1148, 1125, 1084, 873, 840. CD (dioxane) [Į]20 (nm): +11230 (226), 0 (236), - 51000 (240), - 489900 (266), 0

(274), +209200 (282), +510300 (294), +49000 (325), 0 (333), - 56100 (339), 0 (354), +11200 (415). Its identity with

8 was confirmed by MS, 1H- and 13C-NMR, and CD.6-8)

Ustilaginoidin A (5) Isolation and identification will be reported in a forthcoming paper.22) CD (dioxane)

[Į]20 (nm): 0 (222), +133600 (231), + 308400 (261), 0 (275), - 469800 (290), 0 (328), + 48300 (345), + 3100 (425). UV

λdioxanemax nm(ε): 210 (71600), 220 (71400), 250 (40400), 270 (46800), 289 (55300), 329 (4300), 346 (2800), 410 (6400). CD CD spectra were measured in 0.01-0.1 mg/ml dioxane solution using a 100 mm cell on a JASCO J-20 spectropolarimeter.

Acknowledgements The authors thank the members of the Analytical Center of this College for NMR and MS analyses. They are indebted to Dr. S. Udagawa, National Institute of Hygienic Sciences, for the supply of the fungal strains.

References and Notes

1) S. Sekita, K. Yoshihira, and S. Natori, Chem. Pharm. Bull., 28, 2428 (1980). 2) K. Ohtsubo, Proc. Assoc. Mycotoxicol., 12, 28 (1980); idem, ibid., 15, 25 (1982); Y. Ito and K. Ohtsubo, ibid., 16,

22 (1982). 3) The screening was performed under the auspices of the Developmental Therapeutics Program, Division of

Cancer Treatment, National Cancer Institute, Bethesda, Maryland, U.S.A. 4) K. Koyama and S. Natori, Chem. Pharm. Bull., 35, 578 (1987). 5) S. Shibata, A. Ohta, and Y. Ogihara, Chem. Pharm. Bull., 11, 1174 (1963); S. Shibata, Y. Ogihara, and A. Ohta,

ibid., 11, 1179 (1963); S. Shibata and Y. Ogihara, ibid., 11, 1576 (1963); E. Morishita and S. Shibata, ibid., 15, 1765, 1772 (1967).

6) G. Tertzakian, R. H. Haskins, G. P. Slater, and L. R. Nesbitt, Proc. Chem. Soc. London, 1964, 195. 7) M. Matsumoto, H. Minato, E. Kondo, T. Mitsugi, and K. Katagiri, J. Antibiot., Ser. A, 28, 602 (1975). 8) S. T. Carey and M. S. R. Nair, Lloydia, 38, 448 (1975). 9) S. Shibata and Y. Ogihara, Tetrahedron Lett., 1963, 1777.

10) C. P. Gorst-Allman, P. S. Steyn, and C. J. Rabie, J. Chem. Soc., Perkin Trans. 1, 1980, 2474. 11) H. Tanaka, P.-L. Wang, and M. Namiki, Agric. Biol. Chem., 36, 2511 (1972). 12) Unpublished data from our laboratory. 13) A list of final atomic parameters will be sent to the Cambridge Crystallographic Centre. 14) 0. Bastiansen, Acta Chem. Scand., 3, 408 (1949). 15) H. Akimoto and Y. Iitaka, Acta Crystallogr., B25, 1491 (1969). 16) G. Evrard, P. Piret, and M. Van Meerssche, Acta Crystallogr., B28, 497 (1972). 17) I. Goldberg, Acta Crystallogr., B33, 472 (1977). 18) I. Goldberg, Acta Crystallogr., B34, 3387 (1978). 19) N. Harada and K. Nakanishi, Acc. Chem. Res., 5, 257 (1972); N. Harada, S. L. Chen, and K. Nakanishi, J. Am.

Chem. Soc., 97, 5345 (1975); N. Harada, Y. Takuma, and H. Uda, ibid., 98, 5408 (1976); idem, ibid., 100, 4029

(1978). 20) M. Endo and H. Naoki, Tetrahedron, 36, 2449 (1980). 21) S. F. Mason, R. H. Seal, and D. R. Roberts, Tetrahedron, 30, 1671 (1974). 22) The details of the experiments including structure elucidation of the new congeners will be reported in a

forthcoming paper.