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Intramolecular alder ene approach to stereochemical control over three contiguous stereogenic centres : Synthesis of (±)-methyl cucurbate and (±)-methyl epijasmonate
Tetid-nm
L&en, Vol. 35, No. 37, pp. 6907-6%X,1994 Elseviu sciarccIAd Rinted in GmatBritain oo40-4039/94 $7.oo+o.00
6046-4039(94)01412-4
Intramolecular Alder Ene Approach to Stereochemical Control over Three Contiguous Stereogenic Centres : Synthesis of (&Methyl Cucurbate and (&Methyl Epijasmopate TananE sarkar,** Binay K. Ghorai”
and Asoke Banerjib
nt of Chemla~. Indian Institute of Tedudogy. Khmngpur 721302, India;
‘D”r- Bio-Orgenie Dlviaion, Modular I_aboratory.BARE..
Bombay 400036. Indii
Abdrad : The total synthec~iaof ep+mnonoids, (A)-methyl cucurbte nad (+)_methyl ep&tmmnata ia tzbdbad starting fmm aidehyde 14 where the key catupia a hiily +eocontdld S- (3,4) ena cycliition 17 - 18. The epijasmonoid family of natural products feature a. cis .-1, _2- di+ubstitute$ (41 an+ ate .hlgher hyologa 2-4, cyclopentane ring syspm mcludee methyl epUasmon$e methyl tuberonate (61, g-D-glucopyranosyltuberonic ayd (f) and its methyb eater 7 as well aa some of their reduction producta namely, cucurbnz aud (8) and lactone l3. pese substances display a pversity of biological activities, such as strong jasmp note,la* c plant growth t&o-tuber induction and have been targetr of regulation, pheromone synergestl~c and/ r the tuming point in jaemonoid reaearch has intense synthetic interest in recent years. ’ Early been the +iscovery that the characteristic odour of j&mine 1@ ~EIdue to methyl epijaamonate (11 rather than the po alarly known methyl jaamonate (101, and that the real metabolite in jasmonoid biaeyn tEeais is epijasmonic acid (111rather than jasmonid acid (121. In this communication, we describe straightforward syntheses of the methyl ester gtiVb
1 :n= 2 :n= 3 :n= 4 :n= 11: n=
l:Rs 3;Rz 5;R= 7:R= 1 ;R=
Me H H H H
5:R’ = H; R2 = Me 6 : R’ = fi-D-Glu: R2 = H 7 : R’ = t3-D-Glu; R2 I Me
13
8:R=H 9:R=Me
lO:R=Me 12:R=H
of (*I-cucurbic acid (8)‘, a potent plant growth inhibiter and (&methyl epijasmonate (1),‘S6 the queen of aroma, wherein a suitable building block for e ijasmonoid synthesis, e.g. 20, was efficiently prepared in nine steps from 14 via a highly &astereoseAective and diestereoface selective 5-(3,4) ene cyclization of a functionalized 1.6-diene 17 (8cheme). 6907
Scheme ’
14
IS.“: Rl=H;R’=lHP =*d I 16. : R’tlBDPS:R2=H
17
18
TBDPSO
19 : R = CHr
4 20:R=O
21
96% W Huba, 79% 61 08,85% (i) FWPrFBMWW3ii~ -7e” * r.t, 6V% 0 a-BudIF, 8fFN 0 IiSddhr, 7Q%. Tk~alde+$e 14’waa cx+wrkd” the a00duct 17 (31%oven& followiq our eerlk developed protocel. He$ngn.6j+,qohtionofl7m fae+d~tubeunderar at@6? for 18h m.+hly etfecbd carbo&izaticWto 18. 111 almoetquantxtetweyAd. It ehoulN-F be noted #et 18 -tame meet ofthe nec&saty s@reochemwalfeatuh of cucurbicacid (8). @t&miiki.ir$ of Xl3wae lx& carriedout in the presellceof HI ti *ve 1S (79%) which was oxid8tw&1~~~Bti~S0 %I. witkigolefhleti~ acid (69%) ~und&r#&&ee tiditiona followed by w NJ@ gave Wcwgbic m$hyl e$kr.c8) (8Q%)?oo? spectralprdpertlesme & accorda& with thaw reporhd. m, ‘elded(*)- methy aaemonate (1) (70%) ~~~rtif9flrltth~lcacldunq~BrOlP1Cn’s~~llos identifbtl by spectralot@arieoxi ( H- & C-_J@lIQwith tz:oeeofthe au’thentic sainple.Overall yielda of 9 and 1 from 14’kere 12.6%in 11 stepsand,8.8%in’12 stepa,rkqwctively. Achmwbdgum~:We&nnk(=ERRmdBt3T,~oE~
hhn&ng~~~~~&~nb~
thanbMtoFmf.G.~amIRufsT.K&&am [email protected] dautbentic m&yl egeem0nete.Mr.P. Pmdhana3.A.R.C.,Bombqv)iethenkedforhi6h&ldNMB~. Refereneee P Noteq : (a) Niihidn. R: Arree. T. E. J. Aeric. Food Chem. lQ84.54.1001: (b) Babr. T. CL: N&i&. R: Fbbfb. W. L. 1. &&en~e lQl31.iii& l&59; (c)Zd&. J. Chem. Ecol. lQ&, 6, 947;‘(d) kiihidi, R; icree,~ T.- E-i Fukami H. J. &r&z. Food Chem. 1986,S!i, 426. 2. (a) Vi& B. A.; Zimmerman, D. C. Plant Phyiol. lQ84.75, 458; (b) Z&m. Bit&em. Btiphys. Rea. Cbmmun. 1988.111,470. 3. (a) Koda, Y.; Omer, E. A.; Yoohib ara, T.; Shibata, Ii.; Sakamura. 9.; Okazawa, Y. Plant Grit Phyaiol, lQS8,2Q, 1047; (b) Z&m. A&c. Biol. Chem. lQQQ,64 in preenand referencae cited therein. 4. Fukui, H.; Koehimizu, K.; Yamazaki, Y.; Ueuda, S.&k. Bid. Chem. 1977,41,189. 6. Knieer, R; LpmpereLy, D. T&w&&on La#. 1974, B413. 6. (a) Seto. H.; Yoahioka. Ii. ChcmishyLett. 1990, 1797; 6) Kitahara. T.; Miura, IL; Warita, Y.;Takqi, Y.; Mori, K. Agric. B&Z. Ckm. lQ67.61,1129; (c) H&u& en, G.; Gee&A.; Lauer, G.; Urmaan, M.; Friee. J.-w. Chem. Int. Ed Engl. IQQQ,49, 1024; (d) Kitahere, T.; Niehi. T.; Mori, K. Tetmhedmn 19Q1,47. 6999 and refierenceacited therein; (e) Crombie. L; Miatry,K M. J. Chem. Sot. Chem. Cbmmurr lQ88,539; (f) Tanaka, H.; Torii, 5. J. Org. C&m. 1976,40,462. 7. Beetmann. H. J.; Gunawardem N. E. fiyntho8ti 1992 1239. 8. All new compounds were charecterizqd by IR, ‘H- & “C-NM2 and MS. 9. ae determined ae ueunl by GC-MS and NOE etudiee See preceding paper. The iaomeric pq$q of 15 (>QQ%2) on the co-per&n6 dieiil ether Z6 (It = R = SiMesBu3 . 10. GC-MS analyab of crude product indicated the preaenoaof three isomers in a ratio of SQz10.6zO.6. 11. Other reagenta (BFs.2HOAq cone. HCI etc.) were unrewardii. 12. The minor Cl-p isomer (10.6%) cnrrifd over From 18 wan eliminated at this 6bqp prmuma blyby-m formetion to IS. 13. 21 is uncontaminated with any E-bomer.Bd 14. Brown, H. C.; Ge1yr.C. P.; Liu, K. T. J. Org. Chem. 1971, S6.387. 16. QO%pum with 1046of tmne-ephner 10 M determined by “C NMR.” @ec&ed
in UK 26 AprU 19w; rev&ed 18 J&y 1%;
accepted 22 J&y 1994)
L&en, Vol. 35, No. 37, pp. 6907-6%X,1994 Elseviu sciarccIAd Rinted in GmatBritain oo40-4039/94 $7.oo+o.00
6046-4039(94)01412-4
Intramolecular Alder Ene Approach to Stereochemical Control over Three Contiguous Stereogenic Centres : Synthesis of (&Methyl Cucurbate and (&Methyl Epijasmopate TananE sarkar,** Binay K. Ghorai”
and Asoke Banerjib
nt of Chemla~. Indian Institute of Tedudogy. Khmngpur 721302, India;
‘D”r- Bio-Orgenie Dlviaion, Modular I_aboratory.BARE..
Bombay 400036. Indii
Abdrad : The total synthec~iaof ep+mnonoids, (A)-methyl cucurbte nad (+)_methyl ep&tmmnata ia tzbdbad starting fmm aidehyde 14 where the key catupia a hiily +eocontdld S- (3,4) ena cycliition 17 - 18. The epijasmonoid family of natural products feature a. cis .-1, _2- di+ubstitute$ (41 an+ ate .hlgher hyologa 2-4, cyclopentane ring syspm mcludee methyl epUasmon$e methyl tuberonate (61, g-D-glucopyranosyltuberonic ayd (f) and its methyb eater 7 as well aa some of their reduction producta namely, cucurbnz aud (8) and lactone l3. pese substances display a pversity of biological activities, such as strong jasmp note,la* c plant growth t&o-tuber induction and have been targetr of regulation, pheromone synergestl~c and/ r the tuming point in jaemonoid reaearch has intense synthetic interest in recent years. ’ Early been the +iscovery that the characteristic odour of j&mine 1@ ~EIdue to methyl epijaamonate (11 rather than the po alarly known methyl jaamonate (101, and that the real metabolite in jasmonoid biaeyn tEeais is epijasmonic acid (111rather than jasmonid acid (121. In this communication, we describe straightforward syntheses of the methyl ester gtiVb
1 :n= 2 :n= 3 :n= 4 :n= 11: n=
l:Rs 3;Rz 5;R= 7:R= 1 ;R=
Me H H H H
5:R’ = H; R2 = Me 6 : R’ = fi-D-Glu: R2 = H 7 : R’ = t3-D-Glu; R2 I Me
13
8:R=H 9:R=Me
lO:R=Me 12:R=H
of (*I-cucurbic acid (8)‘, a potent plant growth inhibiter and (&methyl epijasmonate (1),‘S6 the queen of aroma, wherein a suitable building block for e ijasmonoid synthesis, e.g. 20, was efficiently prepared in nine steps from 14 via a highly &astereoseAective and diestereoface selective 5-(3,4) ene cyclization of a functionalized 1.6-diene 17 (8cheme). 6907
Scheme ’
14
IS.“: Rl=H;R’=lHP =*d I 16. : R’tlBDPS:R2=H
17
18
TBDPSO
19 : R = CHr
4 20:R=O
21
96% W Huba, 79% 61 08,85% (i) FWPrFBMWW3ii~ -7e” * r.t, 6V% 0 a-BudIF, 8fFN 0 IiSddhr, 7Q%. Tk~alde+$e 14’waa cx+wrkd” the a00duct 17 (31%oven& followiq our eerlk developed protocel. He$ngn.6j+,qohtionofl7m fae+d~tubeunderar at@6? for 18h m.+hly etfecbd carbo&izaticWto 18. 111 almoetquantxtetweyAd. It ehoulN-F be noted #et 18 -tame meet ofthe nec&saty s@reochemwalfeatuh of cucurbicacid (8). @t&miiki.ir$ of Xl3wae lx& carriedout in the presellceof HI ti *ve 1S (79%) which was oxid8tw&1~~~Bti~S0 %I. witkigolefhleti~ acid (69%) ~und&r#&&ee tiditiona followed by w NJ@ gave Wcwgbic m$hyl e$kr.c8) (8Q%)?oo? spectralprdpertlesme & accorda& with thaw reporhd. m, ‘elded(*)- methy aaemonate (1) (70%) ~~~rtif9flrltth~lcacldunq~BrOlP1Cn’s~~llos identifbtl by spectralot@arieoxi ( H- & C-_J@lIQwith tz:oeeofthe au’thentic sainple.Overall yielda of 9 and 1 from 14’kere 12.6%in 11 stepsand,8.8%in’12 stepa,rkqwctively. Achmwbdgum~:We&nnk(=ERRmdBt3T,~oE~
hhn&ng~~~~~&~nb~
thanbMtoFmf.G.~amIRufsT.K&&am [email protected] dautbentic m&yl egeem0nete.Mr.P. Pmdhana3.A.R.C.,Bombqv)iethenkedforhi6h&ldNMB~. Refereneee P Noteq : (a) Niihidn. R: Arree. T. E. J. Aeric. Food Chem. lQ84.54.1001: (b) Babr. T. CL: N&i&. R: Fbbfb. W. L. 1. &&en~e lQl31.iii& l&59; (c)Zd&. J. Chem. Ecol. lQ&, 6, 947;‘(d) kiihidi, R; icree,~ T.- E-i Fukami H. J. &r&z. Food Chem. 1986,S!i, 426. 2. (a) Vi& B. A.; Zimmerman, D. C. Plant Phyiol. lQ84.75, 458; (b) Z&m. Bit&em. Btiphys. Rea. Cbmmun. 1988.111,470. 3. (a) Koda, Y.; Omer, E. A.; Yoohib ara, T.; Shibata, Ii.; Sakamura. 9.; Okazawa, Y. Plant Grit Phyaiol, lQS8,2Q, 1047; (b) Z&m. A&c. Biol. Chem. lQQQ,64 in preenand referencae cited therein. 4. Fukui, H.; Koehimizu, K.; Yamazaki, Y.; Ueuda, S.&k. Bid. Chem. 1977,41,189. 6. Knieer, R; LpmpereLy, D. T&w&&on La#. 1974, B413. 6. (a) Seto. H.; Yoahioka. Ii. ChcmishyLett. 1990, 1797; 6) Kitahara. T.; Miura, IL; Warita, Y.;Takqi, Y.; Mori, K. Agric. B&Z. Ckm. lQ67.61,1129; (c) H&u& en, G.; Gee&A.; Lauer, G.; Urmaan, M.; Friee. J.-w. Chem. Int. Ed Engl. IQQQ,49, 1024; (d) Kitahere, T.; Niehi. T.; Mori, K. Tetmhedmn 19Q1,47. 6999 and refierenceacited therein; (e) Crombie. L; Miatry,K M. J. Chem. Sot. Chem. Cbmmurr lQ88,539; (f) Tanaka, H.; Torii, 5. J. Org. C&m. 1976,40,462. 7. Beetmann. H. J.; Gunawardem N. E. fiyntho8ti 1992 1239. 8. All new compounds were charecterizqd by IR, ‘H- & “C-NM2 and MS. 9. ae determined ae ueunl by GC-MS and NOE etudiee See preceding paper. The iaomeric pq$q of 15 (>QQ%2) on the co-per&n6 dieiil ether Z6 (It = R = SiMesBu3 . 10. GC-MS analyab of crude product indicated the preaenoaof three isomers in a ratio of SQz10.6zO.6. 11. Other reagenta (BFs.2HOAq cone. HCI etc.) were unrewardii. 12. The minor Cl-p isomer (10.6%) cnrrifd over From 18 wan eliminated at this 6bqp prmuma blyby-m formetion to IS. 13. 21 is uncontaminated with any E-bomer.Bd 14. Brown, H. C.; Ge1yr.C. P.; Liu, K. T. J. Org. Chem. 1971, S6.387. 16. QO%pum with 1046of tmne-ephner 10 M determined by “C NMR.” @ec&ed
in UK 26 AprU 19w; rev&ed 18 J&y 1%;
accepted 22 J&y 1994)