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First Total Synthesis of (+)-Secosyrin 1
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TetrahedronLetters, Vol. 38, No. 14, pp.2511-2512, 1997 01997 Elssvier Science Ltd All rights reserved. Printed in Great Britain ow3-4039/97 $1700+ 0.00
Pergamon
PII: S0040-4039(97)00380-8
First Total Synthesis of (+)-Secosyrin 1 Chisato Mukai,* Sameh M. Moharram, and Miyoji Hanaoka* l%eultyof PharmaceuticalSciences,KrmazawaUniversity Takara-machi,Kanazawa920,Japan
total synthesis of (+)-secosyrin 1, isolated from P. syringae.pv. tomato, was Abstract: The first accomplishedin a stereoselectivemanner from diisopropylD-tsrtrate. ‘l%issynthesisunambiguously establishedthe sterewhemisq of (+)-seeosyrin1.0 1997Hsevier Science Ltd.
Secosyrins1 and 2 (1 and2) have a l,7-dioxsspiro[4.4]nonane frameworkand arecoproductsof novel nonproteinaceousC-glycosideelicitorssyringolides1 and 2 (3 and4), isolatedfromP. syringae pv. tcwnato.1 IMonocyclicsyributins1 and 2 (5 and 6) were alsoisolatedfromthe samemedium.lbAlthoughthese simpler four products (1, 2, 5, and 6) are not active elicitors in sharp contrast to structurally more complex syringolides,they are of particularintexestfor understandingtheirbiosyntheticpathway.Syringolideshaveso far been synthesizedby five groups2and the first synthesisof syributin1 (5)2ehas been recordedlately.We describehereinthe first stereoselectivetotal synthesisof (+)-secosyrin1 (1) fromdiisopropylD-tartratein a stereoselectivefashion,whichenabledus to establishits stereochemistryunambiguously.
1 : secoeyrinI(n = 4) 2: secoeyrin2(n = 6)
o 3: eynngolideI(n = 4) 4: syringolide2(n = 6)
5: syributinI(n = 4) 6 : syributin2(n = 6)
The hydroxycompound7,3derivedfromdiisopropyltartrate,was successivelyexposedto oxidation, acetylide addition,and oxidationconditionsto give the ynonederivative8. The rddolreactionof 8 with the lithiumenolateof tert-butylthioacetateeffectedstereoselectiveintroductionof C2-componentto yield9 in 94% yield.It beeameapparentthat the stereochernistryd of the newlyconstructedquatemarycarboncenterof 9 was notin accordancewiththatof 1. Tetrahydrofuranringformationaccompanyingisomerizationof thequatemary chiralcenterwas realizedby takingadvantageof aIkyne-cobaltchetuistry.sUpontreatmentwith C02(CO)8, 9 affordedthe cobalt complex,whichwas subsequentlyexposedto BF3*OEt2in CH2C12at room temperature producing,afterdecomplexation,10 withthe desiredstereochemistryin 74%yieldfrom9 togetherwiththe 2epimer(15%)(10: 2-epimer= 83 : 17). 251I
2512
o BnO,,,, BnOL
BW3,,,
a,b OH OTBDMS — BnO+
7
i!
BnO,,,,
,,.. Y
20 0
BnO
10
Ph
8 OTBDMS
Ph
-b c
*
HClll BnO,,,,““
J
SBut
o SBut
d,e,f —
9
OTBDMS -
‘::&~jL1;::::G::y,.2.. 12: R1 = #=
hexanoyl
Reaefion Condition: (a) 1)Swemoxid.~ phenylacetylene, %uLi,THF,-78”C,S0%(b) Swamoxid.,S0%(c) LHMDS, MeCOSBut,THF,-780C,94%;(d)TBAF-HF,S5%;(e)C02(CO)S, Et@,9S%;(f)1)BFwOEt2,CH2Ck,rt,2) CAN,MeOH, S9%[10(74%)and2-apimer(15%)];(g)Lindiar, Hz,W“ (h)1)03, pyrfdine, CH2C~,2) NaBH4,MeOH,~ DBU,CH2C12, 75%;(i)P&C,Hz,10%HCI,MeOH,90%;(j)hexanoio anhydnde, THF,DMAP,26%[1(70%)and12(25%)]
With 10 possessing proper stereochemistryin hand, the next stage of our synthesis was faced to efficientconstructionof the spiro@ctone moiety.Half-reductionof 10withLindhucatalystfurnishedthecisolefin,ozonolysisof whichwas followedby sua.xxsivetreatmentwithNaBH4and DBUto providethe spiro derivative 11. Finally 11 underwent debenzylationto give the diol, which was acylated with hexanoic anhydrideto give (+)-secosyrin1 (l)[[(x~x+48.2°(c 0.12,CHC13)]6alongwith the diacylatedderivative12. IH-NMRsw~m of syn~etic(+)-secoSyrin1 was in agreementwith that of naturalone.lb TM, we have complete&thefirst total syn@esisof (+)-secosyrin1.7This synthesisdisclosesthat (+)-secosyrin1 shouldbe depicted as (3R,4S,5R)-4-hexanoyloxy-3-hydroxy-l,7-dioxaspiro [4.4]nonan-8-one,while (-)-secosyrin 1 shouldhaveits mirrorform. REFERENCES AND NOTES (1) (a) Midland, S.L.; Keen, N.T.; Sims, J.J.; Midland,M.M.; Stayton, M.M.; Burton, V.; Smith, M.J.; Mazzola, E.P.; Graham, K.J.; Clardy, J. J. Org. Chem. 1993,58, 2940. (b) Midland, S.L.; Keen, N.T.; Sims, J.J. 1 Org. Chem. 1995,60, 1118. (2) (a) Wood, J.L.; Jeong, S.; Salcedo, A.; Jenkins, J. J. Org. Chem. 1995,60, 286. (b) Kuwahara,S.; Moriguchi,M.; Miyagawa,K.; Konno,M.; Kornada,O. Tetrahedron 1995,32, 8809. (c) Henschke, J.P.; Richards, R.W. Tetrahedron Lett. 1996,37, 3557. (d) Ishihara, J.; Sugimoto, T.; Murai, A. Syrdett 1996,335. (e) Honda,T.; Mizutani,H.; Kanai,K. 1 Org. Chem. 1996,61,9374. (3) Mukai, C.; Moharram,S.M.; Kataoka,O.; Hanao@ M. J. Chem. Soc., Perkin Trans. 11995,2849. (4) Compound 9 was efficiently converted into the 5-epimer of 11 by conventional means. X-Ray crystallographicanaIysisof the latter unambiguouslyestablishedits stenxchemistry,therebythe stereochemistryof 9 wasconfiied. Detailsof X-rayanalysiswillbe reportedin somewhereelse. (5) Nicholas, K.M. Ace. Chem. Res. 1987,20,207. (6) No informationon specificrotationof naturalsecosyrin1is available.lb (7) Tieatrnentof (+)-1with lithiumhexamethyldisilazideafforded(+)-syributin1 (5)[[a~0+7.80 (c 0.33, CHC13)][lit.2e [c@+6.8° (c 0.5, CHC13)].Thistransformationcombinedwiththe detailsof this textwill appearas a fullpaperin duecourse. (Received in Japan 3 February 1997; revised 20 February 1997;acceptid 21 February 1997)
TetrahedronLetters, Vol. 38, No. 14, pp.2511-2512, 1997 01997 Elssvier Science Ltd All rights reserved. Printed in Great Britain ow3-4039/97 $1700+ 0.00
Pergamon
PII: S0040-4039(97)00380-8
First Total Synthesis of (+)-Secosyrin 1 Chisato Mukai,* Sameh M. Moharram, and Miyoji Hanaoka* l%eultyof PharmaceuticalSciences,KrmazawaUniversity Takara-machi,Kanazawa920,Japan
total synthesis of (+)-secosyrin 1, isolated from P. syringae.pv. tomato, was Abstract: The first accomplishedin a stereoselectivemanner from diisopropylD-tsrtrate. ‘l%issynthesisunambiguously establishedthe sterewhemisq of (+)-seeosyrin1.0 1997Hsevier Science Ltd.
Secosyrins1 and 2 (1 and2) have a l,7-dioxsspiro[4.4]nonane frameworkand arecoproductsof novel nonproteinaceousC-glycosideelicitorssyringolides1 and 2 (3 and4), isolatedfromP. syringae pv. tcwnato.1 IMonocyclicsyributins1 and 2 (5 and 6) were alsoisolatedfromthe samemedium.lbAlthoughthese simpler four products (1, 2, 5, and 6) are not active elicitors in sharp contrast to structurally more complex syringolides,they are of particularintexestfor understandingtheirbiosyntheticpathway.Syringolideshaveso far been synthesizedby five groups2and the first synthesisof syributin1 (5)2ehas been recordedlately.We describehereinthe first stereoselectivetotal synthesisof (+)-secosyrin1 (1) fromdiisopropylD-tartratein a stereoselectivefashion,whichenabledus to establishits stereochemistryunambiguously.
1 : secoeyrinI(n = 4) 2: secoeyrin2(n = 6)
o 3: eynngolideI(n = 4) 4: syringolide2(n = 6)
5: syributinI(n = 4) 6 : syributin2(n = 6)
The hydroxycompound7,3derivedfromdiisopropyltartrate,was successivelyexposedto oxidation, acetylide addition,and oxidationconditionsto give the ynonederivative8. The rddolreactionof 8 with the lithiumenolateof tert-butylthioacetateeffectedstereoselectiveintroductionof C2-componentto yield9 in 94% yield.It beeameapparentthat the stereochernistryd of the newlyconstructedquatemarycarboncenterof 9 was notin accordancewiththatof 1. Tetrahydrofuranringformationaccompanyingisomerizationof thequatemary chiralcenterwas realizedby takingadvantageof aIkyne-cobaltchetuistry.sUpontreatmentwith C02(CO)8, 9 affordedthe cobalt complex,whichwas subsequentlyexposedto BF3*OEt2in CH2C12at room temperature producing,afterdecomplexation,10 withthe desiredstereochemistryin 74%yieldfrom9 togetherwiththe 2epimer(15%)(10: 2-epimer= 83 : 17). 251I
2512
o BnO,,,, BnOL
BW3,,,
a,b OH OTBDMS — BnO+
7
i!
BnO,,,,
,,.. Y
20 0
BnO
10
Ph
8 OTBDMS
Ph
-b c
*
HClll BnO,,,,““
J
SBut
o SBut
d,e,f —
9
OTBDMS -
‘::&~jL1;::::G::y,.2.. 12: R1 = #=
hexanoyl
Reaefion Condition: (a) 1)Swemoxid.~ phenylacetylene, %uLi,THF,-78”C,S0%(b) Swamoxid.,S0%(c) LHMDS, MeCOSBut,THF,-780C,94%;(d)TBAF-HF,S5%;(e)C02(CO)S, Et@,9S%;(f)1)BFwOEt2,CH2Ck,rt,2) CAN,MeOH, S9%[10(74%)and2-apimer(15%)];(g)Lindiar, Hz,W“ (h)1)03, pyrfdine, CH2C~,2) NaBH4,MeOH,~ DBU,CH2C12, 75%;(i)P&C,Hz,10%HCI,MeOH,90%;(j)hexanoio anhydnde, THF,DMAP,26%[1(70%)and12(25%)]
With 10 possessing proper stereochemistryin hand, the next stage of our synthesis was faced to efficientconstructionof the spiro@ctone moiety.Half-reductionof 10withLindhucatalystfurnishedthecisolefin,ozonolysisof whichwas followedby sua.xxsivetreatmentwithNaBH4and DBUto providethe spiro derivative 11. Finally 11 underwent debenzylationto give the diol, which was acylated with hexanoic anhydrideto give (+)-secosyrin1 (l)[[(x~x+48.2°(c 0.12,CHC13)]6alongwith the diacylatedderivative12. IH-NMRsw~m of syn~etic(+)-secoSyrin1 was in agreementwith that of naturalone.lb TM, we have complete&thefirst total syn@esisof (+)-secosyrin1.7This synthesisdisclosesthat (+)-secosyrin1 shouldbe depicted as (3R,4S,5R)-4-hexanoyloxy-3-hydroxy-l,7-dioxaspiro [4.4]nonan-8-one,while (-)-secosyrin 1 shouldhaveits mirrorform. REFERENCES AND NOTES (1) (a) Midland, S.L.; Keen, N.T.; Sims, J.J.; Midland,M.M.; Stayton, M.M.; Burton, V.; Smith, M.J.; Mazzola, E.P.; Graham, K.J.; Clardy, J. J. Org. Chem. 1993,58, 2940. (b) Midland, S.L.; Keen, N.T.; Sims, J.J. 1 Org. Chem. 1995,60, 1118. (2) (a) Wood, J.L.; Jeong, S.; Salcedo, A.; Jenkins, J. J. Org. Chem. 1995,60, 286. (b) Kuwahara,S.; Moriguchi,M.; Miyagawa,K.; Konno,M.; Kornada,O. Tetrahedron 1995,32, 8809. (c) Henschke, J.P.; Richards, R.W. Tetrahedron Lett. 1996,37, 3557. (d) Ishihara, J.; Sugimoto, T.; Murai, A. Syrdett 1996,335. (e) Honda,T.; Mizutani,H.; Kanai,K. 1 Org. Chem. 1996,61,9374. (3) Mukai, C.; Moharram,S.M.; Kataoka,O.; Hanao@ M. J. Chem. Soc., Perkin Trans. 11995,2849. (4) Compound 9 was efficiently converted into the 5-epimer of 11 by conventional means. X-Ray crystallographicanaIysisof the latter unambiguouslyestablishedits stenxchemistry,therebythe stereochemistryof 9 wasconfiied. Detailsof X-rayanalysiswillbe reportedin somewhereelse. (5) Nicholas, K.M. Ace. Chem. Res. 1987,20,207. (6) No informationon specificrotationof naturalsecosyrin1is available.lb (7) Tieatrnentof (+)-1with lithiumhexamethyldisilazideafforded(+)-syributin1 (5)[[a~0+7.80 (c 0.33, CHC13)][lit.2e [c@+6.8° (c 0.5, CHC13)].Thistransformationcombinedwiththe detailsof this textwill appearas a fullpaperin duecourse. (Received in Japan 3 February 1997; revised 20 February 1997;acceptid 21 February 1997)