Total synthesis of solanoeclepin A

何玉萍2011-06-11

COOHH

H

O

OH

HO

OMeO O

O

a, Potato cyst nematode Globodera rostochiensis. b, Cysts on potato roots, which protect the nematodes until hatch stimulants produced by the host plant are present. c, Potato field affected by potato cyst nematodes.

COOHH

H

O

OH

HO

OMeO O

OA

B

C

D E

F

G

based-inducedintramolecular cyclization

stereoselectiveSimmon-Smith reaction

Coupling reaction

intramolecularDiels-Alder reaction

CN

OAc

m-CPBA

CH2Cl2

CN

OAcO

Me3AlAl(OTf)3

(CH2Cl)2

CN

OAcH O

1) DBU, CH2Cl267% for 3 steps

2) CH2=CHMgBr CeCl3, THF 96%

CN

OH

TBHP, Ti(O-iPr)4

MS 4A, CH2Cl2

92%

CN

OHO

Sharpless 环氧化反应

Meinwald rearrangement

Meinwald rearrangement

Pd(0)/PR3 (5 mol %), Bi(OTf)3·xH2O (0.1 mol %), IrCl3·xH2O (1 mol %), and Er(OTf)3

(1 mol %) hydrgeon migration

CrTPP(OTf), (1 mol %), CrTBPC(OTf ) , (1 mol %) alkyl migration

OR1

R2

H

R3

lewis acid R2

R1

R3

R1R2

O

R3

O

H

Br

Br

Br

Br

O1 mol% CrTPBCOTf

Cl(CH2)2Cl 84℃ 24h

CHO

J. Am. Chem. Soc. 2004, 126, 9554

Chem. Commun., 2009, 1255

Tetrahedron Letters, 2003, 44 , 7687

J . Am. Chem. Soc.,1958, 80, 6303

O

CH3

O

CH3 CH3

CHO

89 : 11

0.1%mol Bi(OTf)3

CH2Cl2

CN

OHO

CN

OH O

N

2 , 6 -lutidine

CN

OTMSO

1) DIBAL, THF2)TBSOTf, 2,6-lutidine CH2Cl293% for 2 steps

3) m-CPBA, (CH2Cl)2

TMSOTf

2, 6-lutidine

(CH2Cl)2

then HF. Py

CN

OTBSTBSO O

LDA then TBSCl, HMPA

THF, 99%

CN

OTBSTBSO

OTBS

1) DIBAL,CH2Cl2

2)(EtO)2P(O)CH2COOEtNaH, THF96% for 2 steps

OTBSTBSO

OTBS

CO2Et

1,2-rearrangement

of the vinyl group

CN

OO-

1) DIBAL, THF

OBuB

O

CONMe2

CONMe2

2)

Et2Zn, CH2I2, CH2Cl2100%, dr = 94:6 OTBS

TBSO

OTBS

CH2OHH

H

Zn/Cu CH2I2 IZnCH2IR3

R4R2

R1

R2 R4

R3R1

IZn I

R2 R4

R3R1

Simmons–Smith reaction

J. Am. Chem. Soc. Vol. 120, No. 46, 1998,11945

OTBSTBSO

OTBS

CO2Et

OTBSTBSO

OH

CH2OBnH

H1) NaH, BnBr TBAI, DMF

2) TBAF, THF 75% for 2 steps

1) o-NO2C6H4SeCNBu3P,THF

2) H2O2, THF 88% for 2 steps OTBS

TBSO

CH2OBnH

H

ArSeCN Bu3P ArSeP+Bu3CN-

ArSeP+Bu3CN- RCH2CH2OH RCH2CH2OPBu3+

ArSe- HCN

RCH2CH2OPBu3+

ArSe- RCH2CH2SeAr Bu3P=O

RCH2CH2SeArH2O2

RCH CH2

H

Se+Ar

O-

RCH CH2 ArSeOH

mechanism

J. Org. Chem., Vol. 40, No. 7, 1975J. Org. Chem., Vol. 41, No. 8, 1976

1) HF.Py, THF2) TBSCl, imidazole DMF

3) DMP, CH2Cl24) HF.Py, THF 86% for 4 steps

CH2OBnH

H

OOH

1) BOMCl, DIPEA TBAI, CH2Cl2

2) t-BuOCH(NMe2)2 DMF

Tf2O 2,6-(t-Bu)2Py

CH2Cl292% for 2 steps

CH2OBnH

H

OOBOM

Me2N

CH2OBnH

H

OTfOBOM

OHC

mechanism

O

NMe2

NMe2t-BuO

O-

NMe2

NMe2t-Bu+O

O

Me2N

Me2NO-

Me2N

Me2+N

H

- t-BuOH

H

- NHMe2

OMe2N

Tf2O

OTf

Me2+N

OHC

OTf

CH2OBnH

H

OTfOBOM

O

MeO

TMS

HOO

MeO

TMS

n-BuLiTHF

1) PPTS DMF, H2O

2) TMSCl imidazole, DMF 94% for 3 steps

CH2OBnH

H

OTfOBOM

O

MeO

TMSO OTMSBu3SnF

PdCl2[P(o-tol)3]2DMF44%

CH2OBnH

H

OBOM

O

MeO

TMSO

O

Hiyama Coupling

OTf

Pd LL

OTf

Bu3SnF

OTMS

O-Sn+Bu3Pd LL

PdLL

O

O

oxidation addition

transmetalation

trans-cisisomerization

reduction elimination

PdL2

OTf-Sn+Bu3O

Me2AlCl

diethyl ether

CH2OBnH

H

OBOM

O

MeO

TMSO

O

CH2OBnH

H

OBOM

TMSO

OMeO O

H

1) CH3COOH, H2O

2) DMP, CH2Cl290%

62% for 2 steps

CH2OBnH

H

OBOM

O

OO O

H

1) SeO21,4-dioxane, H2O

2) Cu(OAc)2

MeOH74% for 2 steps

CH2OBnH

H

OBOM

O

OHO O

O

CH2OBnH

H

OBOM

HO

OMeHO O

O

CH2OBnH

H

OBOM

HO

OMeHO O

OH

IBX

CH2Cl2DMSO

43% for 2 steps

CH2OBnH

H

OBOM

HO

OMeO O

O

DIBAL

toluene

MeI, Ag2O

DMF

97%

CH2OBnH

H

OBOM

O

OMeO O

O

I

COOH oxone(1.3eq)

H2O, 70℃，3h

O

O

I OHO

IBX

Ac2O

O

O

IAcO

DMP

0.5% TsOH80℃

OAcOAc

IO

AcO OAcOAc

O

R1 R2

OH

-AcOH

IO

AcO

O

OO

O

H

R1 R2

IO

OAc

OR1 R2

O

I

OOH

O

O

H

I

OO

O

O

H

H

HH

I

OO

O

O

HH

HH

I

HO

O

O

O

配体交换 扭转 消除

TMSCl

imiazoleDMF90%

CH2OBnH

H

OBOM

TMSO

OMeO O

O

1) OsO4, pyridinet-BuOH

45% (68% based on recoved)

2) NaIO4, CH3CN

TMSCl

imidazoleDMF

70% for 2 steps

CH2OBnH

H

O

OBOM

HO

OMeO O

O

CH2OBnH

H

O

OBOM

TMSO

OMeO O

O

H2

Pd(OH)2

THF

CH3CO2H, H2O

CH2OHH

H

O

O

TMSO

OMeO O

O OH

CH2OHH

H

O

OH

TMSO

OMeO O

O

TMSClimidazole

DMF

88% for 3 stepsthen aq. THF

CH2OHH

H

O

OTMS

TMSO

OMeO O

O

DMP

CH2Cl2

CHOH

H

O

OTMS

TMSO

OMeO O

O

NaClO2, NaH2PO4

2-methyl-2-butene

t-BuOH, H2O

97% for 2 steps

COOHH

H

O

OTMS

TMSO

OMeO O

O

3M HCl

CH3CO2H, H2O

63%

solanoeclepin A

COOHH

H

O

OH

HO

OMeO O

O