Pyrrole Pyrrolidine Piperidine Pyridine and Azepine Alkaloids A. R. Pinder Department of Chemistry Clemson University Clemson South Carolina 29634-1905 U.S.A.* Reviewing the literature published between July 1986 and June 1987 (Continuing the coverage of literature in Natural Product Reports 1987 Vol. 4 p. 527) 1 Pyrrole and Pyrrolidine Alkaloids 2 Piperidine Alkaloids 2.1 Spiropiperidine Alkaloids 3 Pyridine Alkaloids 3.1 Celastraceae Alkaloids 3.2 Sesquiterpenoid Pyridine Alkaloids 3.3 Nicotine Alkaloids 3.4 Azafluorene and Aza-anthracene Alkaloids 3.5 Bis- and Tris-pyridine Alkaloids 4 Azepine Alkaloids 5 References A new abstracting journal Natural Product Updates was launched in January 1987.Issues are published monthly giving highly current coverage of developments in natural products including alkaloids. 1 Pyrroie and Pyrrolidine Alkaloids Pyrrole continues to be a structural feature amongst alkaloids. Several pyrrole-derived amides (pyrrolides) (1) have been isolated from the roots of Achillea ageratifolia. Their structures and configurations have been settled by n.m.r. spectral study; they represent a new series of alkamides.2 Pyrrole-3-carb- amidine (2) has been identified as the lethal principle of the Argentinian poisonous plant Nierembergia hippomanica Miers. Its structure has been arrived at via mass and 'H n.m.r. spectroscopy and corroborated by a simple synthesis addition of sodamide to 3-cyanopyrrole. Hymenidine occurring in several marine sponges is a potent antagonist of serotonergic receptors.Its structure (3) containing both pyrrole and imidazole units has been revealed by spectral st~dy.~ The closely related alkaloid oroidine (4)has been synthesized by two pathways starting with 4-hydroxymethylimidazole (5) (Scheme l).5Funebral (6) is a new lactonic pyrrole alkaloid of the flowers of Quararibea funebris (Llave) Visher; its structure has been assigned on spectral evidence. It is probably the penultimate precursor to the already known funebrine.6 An un-named product C16H20N2010 isolated from above-ground parts of Mercurialis leiocarpa Sieb. et Zucc. proved on X-ray diffraction analysis to be a dimer (7) of a polysubstituted 2-0x0- 3-pyrroline. ' The 13Cand the lanthanide-induced-shift'H n.m.r.spectra of a number of cyclic amides (some of them pyrrolidides and pyrrolideides) that occur in species of Achillea have been recorded. Assignments have been based on spectral com-parisons within the series.8 Four new pyrrolidides (8) have been isolated from A. ageratifolia ; their structures and stereo-chemistry have been settled by 'H n.m.r. infrared and mass spectrometry.2 A new synthesis of trichonine (9) which is an * Address for correspondence Department of Chemistry University of Central Florida Orlando Florida 328 16 U.S.A. Q H -c//o (1) a; R = -I b;R= v H Hymenidine ( 3 ) alkaloid of the leaves of Piper trichostachyon has been described (Scheme 2).' The final product was composed of three geometrical isomers separable by chromatography on alumina ; the (E,E)-component proved to be identical with the natural base and represented 85% of the total yield.67 NATURAL PRODUCT REPORTS 1989 (5) ii ivi 0 Ar N=Ny,NT CHO HN (trans1 1 \iii ArN=Ny.CHO vi .x 1 \ Me2 N02SN iv ( cis + trans ) Oroidine (4) Reagents i p-bromobenzenediazonium chloride pH 8 at room temperature for 2 hours; ii activated MnO, dioxan; iii Me,NSO,Cl Et,N CH,Cl, reflux for 5 hours; iv tributylvinylphosphonium bromide phthalimide NaH THF for 1 hour; v N,H, EtOH at 95 "C for 3 hours; vi 2,3-dibromopyrrole-5-carbonylchloride 4-(dimethylamino)pyridine CH,Cl, pyridine ;vii formamidinosulphinic acid MeOH reflux for 24 hours; viii tritylation; ix BuLi PhN, THF at -5 "C to room temperature; x HCl pH 1 reflux for 18 hours Scheme 1 u CH2OH Funebral (6) 0 II d;R= -''='/ NATURAL PRODUCT REPORTS 1989-A.R. PINDER 69 i,ii CH3[CH2], CH SO Ph -iii t 0 CH ICH21 \\ OHC 14-(10) Trichonine (9) E,E + (E,Z)-and (Z,E) -isomers [85 :10:5] Reagents i BuLi at 0 "C then aldehyde (lo) at -78 "C; ii Ac,O pyridine; iii ButOK ButOH for 12 hours at room temperature (double elimination) Scheme 2 -CHO FCHO -Br iv __c Ncno I Br Ph Me [CH,]6..rPyBUn v 111 H .<OH -vii vi -R-*fNYBun b Reagents i HCHO NaHSO, then KCN H,O; ii HBr CH,CI, at 0°C for 3 hours; iii CH,Cl, 4.& molecular sieve heat for 1 hour; iv LiNPr', THF at -78 "C for 2 hours ;v LiNPr', TMEDA THF at -78 "C for 30 minutes then n-C,H,,Br at -78 "C for 2 hours ; vi Li NH (liq.) THF EtOH at -40 "C for 5 minutes; vii Bu"MgBr Et,O at room temperature for 30 minutes; viii H (50 p.s,i.) 10% Pd/C AcOH for 6 hours Scheme 3 (S)-Pyroglutamic acid (1 1) has been used as the starting Another such alkaloid (+)-trans-2-n-butyl-5-n-heptylpyrrol-point in stereoselective syntheses of cis-and trans-2,5-dialkyl- idine (12) has been synthesized by a new route (Scheme 3).pyrrolidines ;unfortunately the sequence failed when applied The Birch reduction step (vi) proved to be remarkably to trans-2-ethyl-5-n-heptylpyrrolidine, which is an alkaloidal stereospecific.l' component of the venom of ants of the genus Solenopsis.l0 The potent and specific glucosidase inhibitors 1,4-dideoxy- NATURAL PRODUCT REPORTS 1989 I ,II 111 ... ... HOqCMe D-Xylose several O9-OMe -steps 3- 'OH ,-* HO (A) 1 iv iii,vii o-& f-v,vi -Troa-oMe Me0 HO N3 I PhCH20p OMe PhCH20.. OCHzPh ... viii iii.vii 111 ___c __c (A) -OH PhCHzO OCHzPh PhCHZO c -v. xi ($c:CH2Ph dimesylate H H N3 OMS (14) Reagents i (CF,CO),O pyridine; ii NaN,; iii H,O+; iv TsCl pyridine; v H, Pd/C; vi NaHCO, PhCH,OC(O)Cl; vii NaBH,; viii PhCH,Br Ag,O; ix MeSO,Cl pyridine; x NaN, DMF; xi spontaneous cyclization Scheme 4 H I " But 0 R R (77'/o) (23OIO ) vii,viii V I Cbz (+) -Anisomycin (15) Reagents i heat in toluene; ii BusLi THF-hexane at -110 "C; iii p-methoxybenzyl chloride; iv N,H on mixture; v PhCH,OC(O)Cl CH,Cl, Et,N at 25 "C; vi HClO, at 0 "C N-iodosuccinimide KOH; vii H, Pd/C MeOH; viii F,CCO,Na F,CCO,H at 120 "C; ix PhCH,OC(O)Cl THF Na,CO,; x Cl,CCH,OC(O)Cl 4-(dimethylamino)pyridine CH,Cl,; xi Ac,O 4-(dimethylamino)pyridine CH,Cl,; xii Zn HOAc at room temperature; xiii H, Pd/C Scheme 5 NATURAL PRODUCT REPORTS 1989-A.R. PINDER 71 PhCH2 OMe PhCH20WoMe 0MOMO MOMO ' (-1 -Codonopsinine (16) (17) MOM =CH20Me (18) MOM = CH2 OMe 0 Lilaline (19) (20) n I n II I OH .-I 0- A+[( H J iii Solenopsin A (21) Reagents i HgO; ii H,C=CH[CH,],CH, CHCl, at 50 "C; iii Zn HOAc; iv conversion into phenoxythioxocarbonate; v Bu,SnH Scheme 6 1,4-imino-r>- and -L-arabinitol [(13) and (14)]have both been synthesized from D-xylose (Scheme 4).The former occurs in Arachniodes standishii and in Angylocalyx boutiqueanus ;it is the more powerful.12 The 'unnatural ' (+)-enantiomer (1 5) of the alkaloidal antibiotic anisomycin has been synthesized (Scheme 5) from 2,5-dihydropyrrole.l3 The stereostructure of natural (-)-codonopsinine has been revised to (2R,3R,4R,5R) as in (16) on the basis of chemical correlations nuclear Overhauser effects and X-ray diffraction analysi~.'~ This revelation does not invalidate a synthesis of the (+)-enantiomer described earlier ;15 it simply requires that the stereochemistry of the intermediate (1 7) be revised to (1 8).An X-ray examination of this intermediate has corroborated this change.14 Full details of this earlier briefly reported synthesis have now been published and several diastereomers of the codonopsinine structure described.l6 (+)-Lilaline (19) is a new flavonoid alkaloid that has been isolated from flowers of Lilium candidum. It is the first example of a pyrrolidino-flavonol and represents the fifth base of this group to be isolated. Its structural assignment is based entirely on spectral study." Further synthetic studies on the cytochalasans leading to a precursor of cytochalasin H have been described.'* The success of this venture was dependent on a highly stereoselective nucleophilic attack by a Grignard reagent on one (unhindered) face of the carbonyl group C-1 8.18 2 PiPeridine Alkaloids Piperidine bases are reviewed in the latest edition of a well- known monograph.l9 The 13C and lanthanide-induced-shift 'H n.m.r. spectra of several cyclic amides (piperidides and piperideides) have been recorded and specific assignments made.* A new piperidide dehydropipernonaline has been isolated from the fruit of Piper longum L. It is a coronary vasodilator and has been formulated as (20) on spectroscopic evidence.,O Several new syntheses of the fire-ant-venom alkaloid solenopsin A (21) have been reported. One of these (Scheme 6) involves cycloaddition of an alkene to a 2-alkyl-2,3,4,5-tetrahydro-pyridine N-oxide followed by reductive cleavage of the isoxazolidine that is formed; it leads to the racemic base.21 A second route also leading to the racemate has been re- NATURAL PRODUCT REPORTS 1989 Ph.Ph vii 1 (+) -Solenopsin A (21) + 6 -epimer Reagents i LiNPr', CH,I THF at -78 "C for 2.5 hours; ii Zn(BH,), AgBF, THF at -78 "C for I hour; iii PrMgBr Et,O at -60 "C for 20 hours; iv H, Pd/C MeOH; v Me,SiCN ZnBr, CH,Cl, heat for 15 hours; vi LiNPr', THF-HMPA CH,[CH,],,Br at -20 "C for 15 hours; vii HF (aq.) CH,CN; viii NaBH, MeOH at -10 "C for 2 hours Scheme 7 HHH (-) -Andrachamine (24) fco2Me 0si Me3 Ts/N iii n SOzPh iv v iiv,v (25 1 (26) n n 00 PhSO 2 2PhSOz/-00 (B) (C 1 Reagents :i see ref. 29 ;ii Ph,P N-bromosuccinimide (see ref. 30) ;iii BuLi THF (B) -78 "C ;iv sodium amalgam Na,HPO, MeOH ;v HCI MeOH; vi BuLi THF (C) at -78 "C Scheme 8 NATURAL PRODUCT REPORTS 1989-A.R. PINDER a (+I -Sedamine (27) ( 28) ... 111 __c 'it I OH HO H (29;R = H) (32) vii (separated) viii,v 1 I v on (-1 -enant iorner RH (30;R=H) ( resolved ) Me0 ..-t (31 I Reagents i m-ClC,H,CO,H CHCl, at 0 "C; ii heat (Cope elimination); iii HgO CHCl, at 0 "C; iv (D)+(E)+styrene CHCl, reflux for 3 hours; v H, Raney nickel; vi O.lN-HCl (as.);vii NaBH, MeOH at -10 "C; viii MeI; ix inversion at C-8; x HCHO MeOH; xi LiAlH, xii KBH(i-C,H,,),. Scheme 9 ported briefly earlier ;22 full details have now been described.23 A third synthesis which is the first leading to the natural (+)-alkaloid begins with an isoxazolidine that had been synthesized earlier2 (Scheme 7).Treatment of the intermediate (22) as shown afforded (-)-dihydropinidine (23) as an (-)-Andrachamine is a new alkaloid of the shrub Andrachne aspera Spreng. Its structure and relative configuration have been established as (24) by spectral analysis. Application of Horeau's procedure suggests that the configurations of both CH(0H) carbons are S and points to (24) as the absolute configuration.26 The same workers have also isolated (-)-andrachcine from the same source; it is 3,4-didehydro-andrachamine. A simple catalytic hydrogenation would confirm this relationship. 27 An improved synthesis of (+)-isoprosopinine B (26) and the first synthesis of (+)-isoprosopinine A (25) have been reported. In these endeavours a superior method for construction of the side-chain has been devised involving the intermediacy of sulphones and a new procedure for deprotection of N-tosylpiperidines has been discovered (Scheme 8).28 A stereoselective a-amidoalkylation reaction has been used in a synthesis of (+)-sedamine (27) i.e.the enantiomer of the natural alkaloid In essence the strategy involved the expected observation that the chiral appendix adjacent to the nitrogen in the iminium ion (28) would direct the approach of a nucleophile along one of two paths resulting in stereoselective formation of a bond at C-2. Removal of the chiral group would then yield a chiral2-substituted ~iperidine.~ Three new alkaloids have been separated from Sedum acre ;their structures and configurations have been settled by spectral measurements and by a synthetic pathway (Scheme 9) leading to the enantiomers of two of them and the racemate of the third.The natural bases are NATURAL PRODUCT REPORTS 1989 Pseudodistomine A Z(33) R =Me[CH2] CH- -CH 6 - Pseudodistomine B E(34) R = Me[ CH2I6 CH=CH - n V -\ Me H OCOPh H (+) -Dumetorine (35) Reagents i Zn; ii 3,4,5,6-tetrahydropyridineN-oxide; iii Me1 ; iv Zn HOAc; v Mitsunobu inversion (see ref. 34) ; vi saponification ; vii HCO,H heat Scheme 10 MeN I I vi i,viii I H' H! (t)-Tecomanine (36) Reagents i NaOH MeOH for 3 hours then H,O; ii Jones oxidation for 3 hours; iii HOCH,CH,OH H' benzene; iv LiAlH, THF at 0 "C for 5 hours; v MeSO,Cl Et,N CH,Cl, at 0 "C for 10 minutes; vi MeNH, MeOH Na,CO, reflux for 3 hours; vii N-chlorosuccinimide CH,Cl, at 0 "C for 3 minutes; viii Ag,O dioxan (aq.) reflux for 2 hours; ix 60% HClO, acetone for 2 hours Scbeme 11 (-)-3-hydroxynorallosedamine (30; R = H) [the (+)-enanti- omer being obtained by resolution of the synthetic product] (-)-3-hydroxyallosedamine (30; R = CH,) (synthesized as the racemate) and (-)-5-hydroxysedamine [ent-(31)] the (+)-enantiomer (3 1) being reached by resolving the intermediate (32) and proceeding with the (-)-enantiomer as ~utlined.~ Pseudodistomines A and B are two novel antineoplastic bases that occur in an Okinawan tunicate Pseudodistoma kanoko.Their structures (33) and (34) respectively have been deduced from spectral data.The bases appear to function biologically by inhibiting the activity of calmodulin which is a principle that is involved in the proliferation of cells.33 A stereospecific synthesis of the lactonic alkaloid (+)-dumetorine (39 which occurs in the tubers of Dioscorea dumetorum Pax has been effected (Scheme 10). It confirms the structure and ~tereochemistry.~~ A new synthesis of (+)-tecomanine (36) has been published (Scheme 11). It starts from (-)-carvone and involves a Favorskii-type rearrangement of its epoxide to a chiral cyclopentane as intermediate.3s 75 NATURAL PRODUCT REPORTS 1989-A. R. PINDER i NC NC CHzPh 8)- NHCHzPh J p+* CHzPh 1:l CH2 Ph (separated) 1.' lvi CF CP H H Nitramine (37) Isonitramine (38 ) Reagents; i HOCH,CH,OH H+;ii LiAlH,; iii benzoylation; iv HCHO MeOH HCI; v NaBH,; vi HCO,NH, Pd/C MeOH reflux Scheme 12 ii ,iii -H OCHzOMe OCH20Me liv viii Me Me ix x,xi __c __t d' OMe H.<OH (+)-Sibirine (39) several steps .4NMe c CP H H (-) -Sibirine (40) Reagents i K NH (liq.) ButOH Br[CH,J,Cl; ii HCl MeOH; iii CICO,Me NaHCO, CH,Cl,; iv H, Pd/C EtOAc; v HC(OMe), H,SO, MeOH; vi NaN, phase-transfer reaction H,O; vii NaBH, phase-transfer reaction H,O; viii NaH THF MeI; ix homogeneous hydrogenation; x EtSH AICI, CH,Cl,; xi LiAlH, THF Scheme 13 2.1 Spiropiperidine Alkaloids natural bases and of the related alkaloid (-)-sibirine (40) Additional syntheses of racemic nitramine (37) and isonitramine (from Nitraria sibirica) have been settled by enantioselective (38) via an intramolecular Mannich reaction have been syntheses.(+)-Sibirine (39) was reached as outlined in Scheme reported (Scheme l2).,' The absolute configurations of the two 13; the natural base (40)was obtained by a closely similar NATURAL PRODUCT REPORTS 1989 Nudiflorine (42) Reagents i NH (liq.) KMnO, at -33 "C for 4 hours; ii KOH (aq.) heat for 4 hours; iii POCI, at 12&125 "C for 2 hours Scheme 14 RC -1 (45)R ='\ Triptofordinine A ,C=c /H H Ph 1 ,Ph Triptofordinine A -2 (46) R = \ c =c Acanthothamine (4 3) Mayteine (44) H' H (47) (48) iii + several isomers I (separable by t.1.c. and h.p.l.c.1 Me Reagents i pyrrolidine TsOH; ii 4-methyl-l,2,3-triazine,CHCI, at 100 "C in a sealed tube for 2 hours; iii H,C =CHCHMeONH, NaOAc EtOH; iv thermolysis at 180 "C for 40 hours in a sealed tube Scheme 15 pathway starting with the benzoxazepinone (41).Natural (+)-nitramine and (-)-isonitramine (the enantiomer of the natural base) were synthesized by similar routes.3s A new synthesis of (+_)-perhydrohistrionicotoxin,via a ring- contraction of a tetrahydroazepine has been described.39 The azaspiroundecane ring-system of the alkaloid has been syn- thesized stereoselectively from (+)-glutamic acid; in the final product three of the four chiral centres have been estab- lished.,O Two stereocontrolled syntheses leading to depentyl- perhydrohistrionicotoxin have been documented ; they repre- sent two more formal total syntheses of the Carbohydrate starting materials have been used in the synthesis of the 1-azaspir0[5S]undecane ring-system of this group., 3 Pyridine Alkaloids Pyridine alkaloids have been included in a recent review.19 A new synthesis of nudiflorine (42) which is an alkaloid of Trewia nudiJEora L.has been reported; it takes advantage of the unexpected behaviour of a pyridinium salt when an attempt was made to iminate it with liquid ammonia and potassium permanganate (Scheme 14).43 3.1 Celastraceae Alkaloids Four new bases of this subgroup have been isolated. Acantho- thamine occurring in the stems of the Mexican plant Acanthothamnus aphyllus has been formulated as (43) largely from spectral data.44 Mayteine is found in the root of Maytenus guianensis an Amazonian tree.It has been assigned structure (44) on similar evidence.45 Triptofordinines A-1 and A-2 two new alkaloids of this family from Tripterygium wilfordii have been assigned structures (45) and (46) respectively largely as a result of a detailed two-dimensional n.m.r. 3.2 Sesquiterpenoid Pyridine Alkaloids Two new syntheses of guaipyridine (47) and epiguaipyridine (48) which are alkaloids of patchouli oil have been described (Scheme 15).*' 77 NATURAL PRODUCT REPORTS 1989-A. R. PINDER 0 (+) -Sesbanimide A (49) H Scaevodimerine A (50) Scaevodimerine C (52) Chalciporone (55) R = C(0)Et Norchalciporyl propionate (56) R = OC(0)Et 3.3 Nicotine Alkaloids The photo-induced electron-transfer oxidation of nicotine has been explored.It leads to nicotyrine cotinine and dehydro- n~rnicotine.~~ 3.4 Azafluorene and ha-anthracene Alkaloids Three new 1 -azafluorenone alkaloids along with the known onychine have been isolated from the trunkwood of the Brazilian tree Guatteria dielsiana ;they are 6-methoxyonychine dielsine and dielsinol. Dielsiquinone from the same source belongs to a new class of quinones; it is a 1-aza-anthraquinone. All have been formulated on spectral evidence.4n Kinabaline is another azafluorenone alkaloid from the rain-forest tree Meiogyne virgata. Its structure follows from spectral studies and comparison^.^^ 3.5 Bis- and Tris-pyridine Alkaloids Syntheses of orellinine and orelline these being two photo- chemical transformation products of orellanine (the toxic principle of the fungus Cortinarius orellanus) have been described.Improvements on an earlier synthesis of orellanine have been achieved.51 Full details of a previously reported H Scaevodimerine B (51) R = H2 Scaevodimerine 0 (53) R = 0 Sampangine (54) -TR Isochalciporone ( 57) R = CH2 CH 2 C(0)Et E Dehydrochalciporone ( 58) R = CH=CHC(O)Et synthesis of (-)-sesbanimide A (the enantiomer of the natural alkaloid) have been furnished and the procedure has been applied to the synthesis of natural (+)-sesbanimide A (49) starting with D-xylose. 52 Four new dimeric monoterpene alkaloids have been isolated from the New Caledonian shrub Scaevola racernigera Daniker. They are scaevodimerines A B C and D which have been formulated as (50) (51) (52) and (53) on spectral evidence and on interconversions ;all are derived from 2,7-na~hthyridine.~~ Another similarly constituted new alkaloid is sampangine isolated from the stem-bark of the Indian shrub Cananga odorata Hook.Spectral evidence points to structure (54).54 4 Azepine Alkaloids The azepine ring-system has now joined others as a structural feature of a group of natural bases. Four such compounds have been isolated from the pungent mushroom Chalciporus piper- atus which is distinguishable from other boletes by its peppery taste and yellow stem base. The bases are chalciporone (59 norchalciporyl propionate (56) isochalciporone (57) and dehydrochalciporone (58).The presence of an azepine ring and the nature of the side-chain in each compound were deduced from careful spectral analysis.55 5 References 1 Natural Product Updates Royal Society of Chemistry London England. 2 H. Greger C. Zdero and F. Bohlmann Phytochemistry 1987,26 2289. 3 C. A. Buschi and A. B. Pomilio Phytochemistry 1987 26 863. 4 J. Kobayashi Y. Ohizumi H. Nakamura and Y. Hirata Experi-entia 1986 42 1176. G. de Nanteuil A. Ahond C. Poupat 0.Thoison and P. Potier Bull. SOC. Chim Fr. 1986 813. 6 T. M. Zennie J. M. Cassady and R. F. Raffauf J. Nat. Prod. 1986 49 695. 7 Y. Masui C. Kawabe K. Matsumoto K. Abe and T. Miwa Phytochemistry 1986 25 1470. 8 0.Hofer H. Greger W. Robien and A. Werner Tetrahedron 1986 42 2707.9 T. Moriyama T. Mandai M. Kawada J. Otera and B. M. Trost J. Org. Chem. 1986 51 3896. J. L. Marco J. Heterocycl. Chem. 1986 23 1059. 11 P. Q. Huang S. Arseniyadis and H.-P. Husson Tetrahedron Lett. 1987 28 547. 12 G. W. J. Fleet and P. W. Smith Tetrahedron 1986 42 5685. 13 A. 1. Meyers and B. Dupre Heterocycles 1987 25 113. 14 H. Iida N. Yamazaki C. Kibayashi and H. Nagase Tetrahedron Lett. 1986 27 5393. H. Iida N. Yamazaki and C. Kibayashi Tetrahedron Lett. 1985 26 3255. See Nat. Prod. Rep. 1986 3 171 for synthesis outline (Scheme 2). 16 H. Iida N. Yamazaki and C. Kibayashi J. Org. Chem. 1987,52 1956. 17 I. Masterova D. Uhrin and J. Tomko Phjttochemistry 1987,26 1844. 18 R. Sauter E. J. Thomas and J. P. Watts J.Chem. Soc. Chem. Commun. 1986 1449. 19 M. Sainsbury in “Rodd’s Chemistry of Carbon Compounds ” 2nd edn. Vol. IVC (Supplement) ed. M. F. Ansell Elsevier Amsterdam 1987 p. 169. N. Shoji A. Umeyama N. Saito T. Takemoto T. Kajiwara and Y. Chizumi J. Pharm. Sci. 1986 75 1188. 21 W. Carruthers and M. J. Williams J. Chem. SOC. Chem. Com- mun. 1986 1287. 22 See Nat. Prod. Rep. 1986 3 171 (Scheme 9). 23 R. Yamaguchi Y. Nakazono T. Matsuki E. Hata and M. Kawanisi Bull. Chem. SOC. Jpn. 1987 60,215. 24 See Nat. Prod. Rep. 1985 2 181 (Scheme 5). D. S. Grierson J. Royer L. Guerrier and H.-P. Husson J. Org. Chem. 1986 51 4475. 26 V. U. Ahmad and M. A. Nasir Heterocycles 1986 24 2841. 27 V. U. Ahmad and M.A. Nasir Phytochemistry 1987 26 585.28 T. N. Birkinshaw and A. B. Holmes Tetrahedron Lett. 1987 28 813. NATURAL PRODUCT REPORTS 1989 29 A. B. Holmes J. Thompson A. J. G. Baxter and J. Dixon J. Chem. Soc. Chem. Commun. 1985 37. 30 S. Hanessian M. M. Ponpipom and P. Lavalee Carbohydrate Res. 1972 24 45. 31 K. T. Wanner and A. Kartner Heterocycles 1987 26 921. 32 W. Ibebeke-Bomangwa and C. Hootelk Tetrahedron 1987,43,935. 33 M. Ishibashi Y. Ohizumi T. Sasaki H. Nakamura Y. Hirata and J. Kobayashi J. Org. Chem. 1987 52 450. 34 0.Mitsunobu and M. Eguchi Bull. Chem. SOC. Jpn. 1971 44 3427. 35 A. S. Amarasekara and A. Hassner Tetrahedron Lett. 1987 28 3151. 36 T. Kametani Y. Suzuki C. Ban and T. Honda Heterocycles 1987 26,1491. 37 W. Carruthers and R. C. Moses J.Chem. Soc. Chem. Commun. 1987 509. 38 P. J. McCloskey and A. G. Schultz Heterocycles 1987 25 437. 39 P. Duhamel M. Kotera and T. Monteil Bull. Chem. SOC. Jpn. 1986 59 2353. 40 J. D. Winkler P. M. Hershberger and J. P. Springer Tetrahedron Lett. 1986 27 5177. 41 D. Tanner and P. Somfai Tetrahedron 1986 42 5657. 42 K. Brewster J. M. Harrison T. D. Inch and N. Williams J. Chem. SOC. Perkin Trans. I 1987 21. 43 D. J. Buurman and H. C. van der Plas J. Heterocycl. Chem. 1986 23 1015. 44 A. A. Sanchez J. Cardenas M. Soriano-Garcia R. Toscano and L. Rodriguez-Hahn Phytochemistry 1986 25 2647. 45 J. R. de Sousa J. A. Pinheiro E. F. Ribeiro E. de Sousa and J. G. S. Maia Phytochemistry 1986 25 1776. 46 Y. Takaishi K. Ujita H. Noguchi K.Nakano T. Tomimatsu S. Kadota K. Tsubono and T. Kikuchi Chem Pharm. Bull. 1987 35 3534. 47 T. Okatani J. Koyama K. Tagahara and Y. Suzuta Hetero-cycles 1987 26 595; T. Okatani J. Koyama J. Tagahara Y. Suzuta and H. Irie ibid. p 925. 48 S. Yamada T. Sakai and M. Ohashi Heterocycles 1987 25 287. 49 M. 0.F. Goulart A. E. G. Santana A. B. De Oliveira G. G. De Oliveira and J. G. S. Maia Phytochemistry 1986 25 1691. 50 D. Tadic B. K. Cassels M. Leboeuf and A. Cavk Phyto-chemistry 1987 26 537. 51 M. Tiecco Bull. Soc. Chim. Belg. 1986 95 1009. 52 M. J. Wanner N. P. Willard G.-J. Koomen and U. K. Pandit Tetrahedron 1987 43 2549. 53 A.-L. Skaltsounis F. Tillequin M. Koch J. Pusset and G. Chauviere Heterocycles 1987 26 599. 54 J. U. M. Rao G.S. Giri T. Hanumaiah and K. J. V. Rao J. Nat. Prod. 1986 49 346. 55 0.Sterner B. Steffan and W. Steglich Tetrahedron 1987 43 1075.