robert e ireland - scripps research institute · the career of robert e. ireland 08/22/2015...
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Baran LabGroup Meeting
Herrmann08/22/2015The Career of Robert E. Ireland
Biography- Born 1929 - Died February 3, 2012 (Aged 82)
Education- A.B. (1951) Amherst College - Ph.D. (1954) from University of
Wisconsin Madison under William Summer Johnson
- Post-Doc (1954-1956) at UCLA under William Gould Young
Academic Career1956 - Professor of Chemistry at University of Michigan 1965 - Professor of Chemistry Caltech 1985 - Director of the Merrell-Dow Research Institute (Strasbourg, France) 1986 - Chairmen/Thomas Jefferson Professor of Chemistry at the University of Virginia 1995 - Emeritus status at the University of Virginia
Awards and HonorsNSF Postdoctoral Fellow (1954-56) Fellow of the Alfred P. Sloan Foundation (1962) ACS Ernest Guenther Award (1977) ACS Award for Creative Work in Synthetic Organic Chemistry (1988)
Research Interest1950s: steroids, total synthesis 1960s: tricyclic diterpenes, pentacyclic triterpenes, total synthesis 1970s: ester enolate claisen rearrangements, terpenoid antibiotics, reductive deoxygenation of alcohol and ketones, synthesis of furanoid and pyranoid glycals, total synthesis 1980s: ester enolate claisen rearrangements, terpenoid antibiotics, polyether antibiotics, spiroketal formation, total synthesis 1990s: ester enolate claisen rearrangements, mechanistic investigations, macrolide synthesis, total synthesis
Ireland Lectureship (University of Virginia)
Top Cited Papers1. “Ester Enolate Claisen Rearrangement - Stereochemical Control Through
Stereoselective Enolate Formation.” J. Am. Chem. Soc. 1976, 98, 2868. (988 citations) 2. “An Improved Procedure for the Preparation of the Dess-Martin Periodinane.”
J. Org. Chem. 1993, 58, 2899. (643 citations) 3. “Claisen Rearrangement of Allyl Esters.” J. Am. Chem. Soc. 1972, 94, 5897. (357 citations) 4. “Application of the Swern Oxidation to the Manipulation of Highly Reactive
Carbonyl Compounds.” J. Org. Chem. 1985, 50, 2198. (279 citations) 5. “Stereochemical Control in the Ester Enolate Claisen Rearrangement. 1.
Stereoselectivity in silyl ketene acetal formation.” J. Org. Chem. 1991, 56, 650.
(243 citations)
130+ publications in scientific journals1 book (Organic Synthesis)
Interesting FactsOutside interest: horse racing, fine wines, fast cars, good scotch, and needlepoint
“Bob’s lucid and invariably entertaining lectures in the classroom and invited symposia and seminars graphically illustrated the power and beauty of multistage organic synthesis and inspired generations of chemists, both young and old. His former students and postdoctoral associates have become successful chemists themselves…Chemistry has attracted many colorful practitioners, and Bob may be counted among the best of them…But it is for his many contributions to education and science that he will be long remembered”
-James A. Marshall (JOC 2013, 78, 1-2)
Baran LabGroup Meeting
Herrmann08/22/2015The Career of Robert E. Ireland
Chapter 1: Organic Reactions: “Organic molecules can be broken down into the problem of preparing the carbon framework and that of the introduction, modification, and/or removal of various functional groups.” -carbon-to-carbon bond formation -effect on functional group changes
Ireland Claisen-Rearrangment (Ester Enolate Claisen Rearrangement until 1982)
O
O
R5R1
R3
R2
R4 O
TMSO
R4 R5
R1R3
R2R5
O
R4
OHR3
R2
R1
N-isopropylcyclohexylamine,n-BuLi, THF, -78 °C; TMSCl;25 °C, 30 min
66-88%Ireland, R. E.; Mueller, R. H.; Willard, A. K. J. Am. Chem. Soc. 1976, 98, 2868-2877 (988 citations)
O
O
OEtC5H11
Me
LiICA, TMSClTHF
O
OTMS
OEtC5H11
Me
OEt
TMSO
O
C5H11
Me
OOEt
OMe
C5H11O
Me
C5H11O
Me
C5H11
dihydrojasmone
MsOH, EtOH
70% (2 steps)
aq OH-1. DIBAL-H2. OH-
85%95%
Ireland, R. E.; Mueller, R. H. J. Am. Chem. Soc. 1972, 94, 5897-5898 (357 citations)
Claisen Rearrangment of Allyl Esters (Original Ireland Claisen-Rearrangement)
LDA
Stereoselectivity in Silyl Ketene Acetal Formation
MeO
O
MeO
OLi
O
OLi
Me
MeO
OTBS
O
OTBS
Me
TBSCl( Z )-1( E )
( Z ) ( E )-1
THFTHF/45% HMPA
(Z)-1 : (E)-1 6:94 (88% de)(Z)-1 : (E)-1 93:7 (86% de)
Ireland, R. E.; Wipf, P.; Armstrong III, J. D. J. Org. Chem. 1991, 56, 650-657 (243 citations)Tested the Stereoselectivity of Silyl Ketene Acetal formation:-solvent effect: THF, TMEDA, DMPU, and HMPA (THF favors E; addition of DMPU/HMPA favors Z)-ester to base ratio-base effect: LDA and LHMDS
Me
Me
Me
Me
Me
Ireland Claisen-RearrangementJ. Org. Chem. 1974, 39, 421 (claisen rearrangement of N-allylketene O,N-acetals)J. Org. Chem. 1976, 41, 986 (construction of prostanoid skeleton)Can. J. Chem. 1979, 57, 1743 (generation of C-glycosides)J. Org. Chem. 1980, 45, 48 (enolate claisen rearrangement of esters from furanoid and pyranoid glycals)J. Org. Chem. 1983, 48, 1829 (stereochemistry of the claisen rearrangement)J. Org. Chem. 1991, 56, 3572 (Ireland Claisen-Rearrangement, chairlike vs boatlike transition-state)
TBS
O
Me
MeO
LDA, THF;TBSCl, HMPA,
-78 °C → rt
86%93:7 dr
LHMDS, THF;TBSCl, HMPA
-78 °C
86%94:6 dr
Me
HO2CTBS
Me
Me
HO2CTBS
Me
Me
Me
BnO
Me
Me
BnO
J. Am. Chem. Soc. 1984, 106 , 3668
Asymmetric Induction in the Ester Enolate Claisen Rearrangement
O
OTMSMe
Me
Me
O
OTMS
Me
Me
Me
OH
O
MeMe
MeOH
O
MeMe
Me
THF, 70 °C, 3 h; aq HCl85:15, 70% dr (favoring 2)
THF, 70 °C, 3 h; aq HCl80:20, 60% dr (favoring 3)
( E )
( Z )
2 3
O
OTMSMe
Me
O
OTMS
MeMe
OH
O
MeMe
OH
O
MeMe
THF, 70 °C, 3 h; aq HCl90:10, 80% dr (favoring 4)
THF, 70 °C, 3 h; aq HCl87.5:12.5, 75% dr (favoring 5)
( E )
( Z )
4 5
OSiR3
O
MeMe
OSiR3
O
MeMe
O RMe
MeR3SiO
O R
MeR3SiO MeO
R
OSiR3
MeMe
MeO
R
OSiR3
MeR R
Z-chair TS E-chair TSE-boat TS Z-boat TS
Synlett. 2010, 11 , 1717
Chairlike vs Boatlike Transition State
chair TS preferred
chair TS preferred chair TS preferred
chair TS preferred
Baran LabGroup Meeting
Herrmann08/22/2015The Career of Robert E. Ireland
Chapter 2: Synthetic Design I: Preliminary Planning: “In designing a synthesis, we must think back from the complex to the simple so that, in practice, we may rationally work from the simple to the complex with a suitable map to follow.” -Molecular History -Starting Materials -Key Intermediates
CO2HI
KBrO3, H2SO4
93%I
OO
OHO
Ac2O, 0.5% TsOH,80 °C, 2 h
91%I
OO
OAcOAc
OAc
Ireland, R. E.; Liu, L. J. Org. Chem. 1993, 58, 2899 (643 citations)
Dess-Martin Periodinane Preparation
Used catalytic amount of TsOH in place of HOAc, 91% yield in less than 2 h, 100 g scale, product preciptates completely (no need to evaporate)
Cl O
O
acroleinO
R
OO
OO
nn
n n
n = 1 or 2
[O]
OO
n
OHO
O
OHH H
Chem. Ber. 1981, 114 , 1418
Spiroketal Formation via Hetero-Diels-Alder
On
Cleavage of Spiroketal Intermediates: Studies toward Marcolide Total Synthesis
J. Org. Chem. 1983, 48, 1303
OO
Me
Me
Me
MeO2CH
H
MeHS SH
BF3•OEt
SS
HOCO2Me
MeHO
Me
Me
Me
OTBSCO2Me
MeTBSO
Me
Me
Me
O
Synthesis of Furanoid and Pyranoid Glycals
O
OO OMe
MeHO
1. PPh3; CCl4, THF, 67 °C2. Li-NH3
60%O
OMe
Me
OH
intermediate chloride isinstable at high temp
J. Org. Chem. 1978, 43, 786J. Am. Chem. Soc. 1985, 107 , 3285
O
OO OMe
MeHO
P(NMe2)3, CCl4, THF,-78 °C; Li-NH3
87%O
OMe
Me
OH
J. Org. Chem. 1980, 45, 48
OP
Me2N
NMe2Me2N
Clproposed
intermediate
Preparation of α-Substituted β-Ketoesters
EtO
O
OH
O
REtO
O
O
O
R
2 equiviPrMgBr
THF
Mg
R'COClEtO
O O
R
MgCl
R'EtO
O O
RR'
J. Am. Chem. Soc. 1959, 81, 2907
O
OMe
O
Me
1. Li, NH3, THF2. THF-TMEDA, ClPO(NMe2)2
70% O
OMe
(Me2N)2OPO
Me
H
Li, EtNH2, THFt-BuOH
95% O
OMe
Me
H
Ireland, R. E.; Muchmore, D. C.; Hengartner, U. J. Am. Chem. Soc. 1972, 94, 5098-5100 (208 citations)
O
O
CH2OH
Me
1. n-BuLi, DME, ClPO(NMe2)22. Li, EtNH2, THF, t-BuOH
89% (2 steps)O
O
Me
Me
O
O
Me
O
O
Me H
Me
H H
1. n-BuLi, DME, HMPA, ClPO(NMe2)22. Li, EtNH2, THF, t-BuOH
86% (2 steps)
HO
O
O
Me
O
O
Me H
Me
H H
-alternate to wolff-kischner, direct cleavage of the hydroxyl functional group, two-step process for the reductive removal of a ketone!(tetramethylphosphorodiamidate (TMPDA) group is more necessary fo rthe deoxygenation of primary and secondary alcohols (due to greater ease of formation than a difference in the reduction stage)-diethyl phosphate (DEP) group appears better for the reductive removal of tertiary alcohols
1. n-BuLi, DME, ClPO(OEt)22. Li, EtNH2, THF, t-BuOH
79% (2 steps)
OH
Reductive Deoxygenation of Alcohols and Ketones
Baran LabGroup Meeting
Herrmann08/22/2015The Career of Robert E. Ireland
Chapter 3: Synthetic Design II: Molecular Characteristics: “More than any other scientific endeavor, a synthetic plan is an effort on the part of the organic chemist to put his knowledge of the field to his own use. He must project the results of experiments as yet untried and unite numerous such projections into a cohesive scheme that will accomplish his preconceived goal.” -Molecular Size -Stereochemical Considerations -Carbon Skeletal Complexity -Stereoselectivity -Functionality
H
H
Me
MeMe
Me
(±)-pimaradiene H
H
Me
MeMe
Me
(±)-sandaracopimaradieneH
H
MeMe
Me
DL-germanicol
pentacyclic triterpene
H
Me
Me
Me Me
MeHO
Me
MeMe
H
DL-alnusenone
triterpenes
Me
H
Me
Me Me
MeO
H
Me
H
(±)-friedelin
Me
H
Me
Me Me
MeO
H
MeMe
tricyclic diterpenes
H
Me
fusidic acid
terpenoid antibiotics
H
Me
MeHO
CO2H
OAcHO
MeH
HO
CH2OHH
Me
Me H
OHCH2OH
(±)-aphidioclin
polyether antibiotics
O
OMe
Me
H
HMe
H
OH
OMe
O
H
(+)-streptolic acidCO2H
HO
MeO O
Me
OH
Me
O
Me C2H5
C2H5
Me MeOHlasalocid A (X537A)
chlorothricolide: R1=R2=R3=H(±)-19,20-dihydro-24-O-methylchlorothricolide R1=R2=CH3, R3=CO2C2H5
OO
OO
R2O
OR3
H
H
H
MeCO2R1
Me
H
O
O
OO
O
CO2H
OH
Me
OMe
HO
Me Me
Me
HOCO2HMe
Me Me
12
13
16 17
54
monensin
extra
N
O
OO
O
O
Me
OMe
HO
OMe
Me
OH
MeMeO
HOMe
OMe
FK-506
H
OO
O
MeO
Me Me MeH
H MeH
CO2Htirandamycic acid
H
H
Me
MeMe
Me
(±)-pimaradiene
H
H
Me
MeMe
Me
(±)-sandaracopimaradiene
OMeO
Me
HMeMe
O
N
H
H
OMe
HMeMe
H
HMe
OMe
HMeMe
H
HMe
1 3
1. MeMgBr2. KOtBu (130 equiv) MeI
:
67%
ratio
1. Na, alcohol2. BzCl, py.3. 430 °C
1. Na, alcohol2. BzCl, py.3. 430 °C
62%
64%
J. Org. Chem. 1963, 28, 6Tet. Lett. 1960, 25, 37
DL-alnusenoneJ. Am. Chem. Soc. 1970, 92, 7232 (1st total synthesis)J. Org. Chem. 1975, 40, 1000 (polyene cyclization)
J. Am. Chem. Soc. 1973, 95, 7829
O
MeO
Me
O
OEt
KOH, MeOH
86%
OEt
MeO
Me
O
OEt
MeO
Me
CN
HO
Et3Al, HCN, THF
86%
alternate epimerEt2AlCN, benzene;
KOtBu, t-BuOH90% (epimer)
Me
Me
H
Me
OEt
MeOMe
Me
H
Me
Me Me
Me
H
O
MeO
1. LiAlH42. n-BuLi, DME; HMPA, Et3N, ClPO(NMe2)3
Me
MeMe
H
DL-alnusenone
Me
H
Me
Me Me
MeO
H
Me
Me
H
Me
Me Me
Me
H
O
KOtBuMeI
Baran LabGroup Meeting
Herrmann08/22/2015The Career of Robert E. Ireland
Chapter 4: Wherein the Carbon Skeleton is the Thing: “Tackle the synthetic design by working back, step by step, to starting materials from our desired objective.”
OMe
OO O
O
O
OMe
H
Me
OH
Me
H
Me
HO
O
trans-syn-transJ. Am. Chem. Soc. 1972, 94, 3652
Formation of trans-syn-trans-Perhydrophenanthrene Derivatives
epoxide allowed for trans AB ring
Me
O
O
O
O
OO
O
Me
H
MeH2O2, NaOH, CH2Cl2;
R2NNH2, benzene; H3O+
74%O
O
O
Me
H
MeO
N
Ph
NH2
H
Me
H
Me
MeO
O
J. Org. Chem. 1977, 42, 1267
H
Me
H
Me
MeO
O
1. MCPBA, CH2Cl22. BF3•Et2O, CH2Cl2
33%H
Me
H
Me
Me
OTBS
O
OO
H
OTBS
H
Me
H
Me
MeO
OTBS
MeH
J. Org. Chem. 1977, 42, 1276
H
Me
H
Me
MeHO
CO2H
OAcHO
MeH
1. CH2N22. AcCl, DMAP3. O3, CH3OH, SMe2
H
Me
H
Me
MeAcO
O
OAcAcO
MeH
97%H
Me
H
Me
MeO
OTBS
MeH
fusidic acid (material received from Leo Pharmaceuticals and Hoffmann-La Roch and Co.)
Degradation of Fusidic Acid
OO
O
MeO
Me Me Me
HONH
O
O
H
H MeH
tirandimycin
J. Am. Chem. Soc. 1981, 103 , 3205
OOAc
OAcOAc
H OOTBS
OOBn
H
OMe
1. LHMDS, THF, TBSCl, HMPA, -78 °C to rt; benzene, reflux2. aq HCl, THF
65%, dr 4:1 OH
OBn
OTBS
OO
O
MeO
Me Me MeH
H MeH
CO2Htirandamycic acid
Me
OH
O
O
OOBn
OMe
LHMDS, THF, TBSCl,HMPA, -78 °C to rt;
benzene, reflux; KF•H2O,KHCO3, HMPA; CH3I
85%, dr 86:14 OH
OBn
Me
OMe
O
O
OMe
Me
H
HMe
H
OH
OMe
O
H
(+)-streptolic acidJ. Am. Chem. Soc. 1988, 110 , 854
see Rodriguez Group SeminarJACS Year in Review: 1981 (Rodriguez, 2011)
named reactionmechanism
mechanism
named reaction
mechanismHO
CH2OHH
Me
Me H
OHCH2OH
(±)-aphidioclin
J. Am. Chem. Soc. 1981, 103 , 2446 (total synthesis)J. Org. Chem. 1979, 44, 4318 ([5.4.0]-Bicyclo)J. Org. Chem. 1979, 44, 4323 (spiroannelation)
MeO
TBSO
OCH3 Me
H
O
O
O
Diels-Alder Hetero-Diels-AlderMe
H
O
O
O TMS
Me
H
O
O
O
TMS1. 150 °C2. n-BuLi i-AmONO
NOH
H
Me HO
O
O
1. NH2Cl, THF2. hv, Et2O -75 °C3. silica gel
60%Me H
O
O
O
1. (CH2O)x, C6H5SH, Et3N, EtOH2. Li, NH3, t-BuOH; Et3N, TMSCl
70%Me H
O
O
TMSOMeH
Baran LabGroup Meeting
Herrmann08/22/2015The Career of Robert E. Ireland
Chapter 5: Stereochemistry Rears its Ugly Head: “It is particularly in the total synthesis of natural products that the problem of stereochemistry becomes significant…thus an ideal synthetic scheme must furnish the correct stereoisomer as well as the required skeletal and functional group arrangements.”
O
O
OO
O
CO2H
OH
Me
OMe
HO
Me Me
Me
HOCO2HMe
Me Me
1213
16 17
5 4
monensin
OO
O PhMe
OMe
1. LHMDS, THF, TBSCl, HMPA, -100 °C to rt2. benzene, reflux; LiAlH4
87%, dr 7:1 O
Me O
O
Ph
MeH
HO O
Me OH
Br
MeH
Me
MeO
OMOM
TBSO
1. Dess-Martin ox.; CH2=CHCHO, Et3N2. NaBH4
O
Me
MeH
Me
MeO
OMOM
TBSO
O
OH
38%O
Me
MeH
Me
MeO
OMOM
TBSO
O
CO2H
O
OO
OBnOCOCl
Me OLi
OSEM
1. TBSCl, HMPA, -100 °C; LDA; rt; H3O+
2. LiAlH4
80%, dr 1:1O
OO
BnO O
Me
OSEMHO
H
O
O
O
BnO
O
Me
Me
H OH HMeO
OSEM
Me
Me
O
HO
O
Me
Me
H OH HMeO
OSEM
Me
Me
1. Li-NH32. P(NMe2)3, CCl4; LiDTBB
87%
O
Me
MeH
Me
MeO
OMOM
TBSO
O
O
O
O
O
Me
HOH
OH H
MeO OSEM
Me
Me
TMSCl, HMPA; LDA; CH2N22. W-2 Raney Ni, H2; LiAlH4
14% + 37% C12 epimer
O
O
OO
O
OTBS
OSEM
Me
OMe
MOMO
Me Me
Me
MeOCO2HMe
Me Me
1213
16 17
5 4
lasalocid A (X537A)J. Am. Chem. Soc. 1983, 105 , 1988 (total synthesis)J. Am. Chem. Soc. 1980, 102 , 1155 (studies toward TS)J. Am. Chem. Soc. 1980, 102 , 6178 (studies toward TS)J. Org. Chem. 1983, 48, 5186 (enantiomer total synthesis)
monensinJ. Am. Chem. Soc. 1993, 115 , 7166 (total synthesis)J. Am. Chem. Soc. 1993, 115 , 7152 (synthesis of spiroketal and tricyclic glycal segments)J. Am. Chem. Soc. 1985, 107 , 3271 (synthesis of the monensin spiroketal)J. Am. Chem. Soc. 1985, 107 , 3279 (synthesis of bis(tetrahydrofuran) via ireland claisen)J. Am. Chem. Soc. 1985, 107 , 3285 (approach to synthesis of monensin)
O
Me
OEt
OMOM
1. LDA, TMSCl THF, -78 °C to rt2. CH2N2
O
MeOMOM
MeO
O
HMe O
MeO
BnO
HMe
OMe
OMOM
1. LDA, TMSCl -78 °C to rt2. CH2N2
O
MeBnO
HMe
O OMOM
Me
CO2Me
O
67%, 3:1 drO
MeO
HMe
O
Me
Me
Me
HH
OH
Me
1. LDA, Et2O; ZnCl22. H2, Pd/C, EtOH
34%
Me
HOCO2Bn
CHO
Me
60%, 9:1 dr
CO2HHO
MeO O
Me
OH
Me
O
Me C2H5
C2H5
Me MeOHlasalocid A (X537A)
O
OCO2CH3 Me CCH3Bn2NC
benzene
60-80%
Bn2NCO2CH3 Me
Me
HOCO2Bn
CHO
Me
Me
H
Baran LabGroup Meeting
Herrmann08/22/2015The Career of Robert E. Ireland
Chapter 6: Multistage Synthesis: Logistics and Stereochemistry Combine to Produce Nightmares: “As in any field of intellectual endeavor, synthetic organic chemistry has its monumental achievements. In the realm of synthesis, these efforts have classically been the multistage natural product syntheses.”
MeO
TBDPSO
Me O
Me
OO O
MeMe
O
ON
Me
Me
OMeO
OMeMe
O
O
MeO
TBDPSO
Me O
Me
OO O
MeMe
ON
Me
Me
OMeO
OMeMe
OTES
O
I
1. C8K, ZnCl2AgOAc2. DMDO3. HF, MeCN 17%
N
O
OO
O
O
Me
OMe
HO
OMe
Me
OH
MeMeO
HOMe
OMe
1. NaOCl, KBr, NaHCO3; NaH2PO4, NaClO2; CH2N22. Dess-Martin Ox.3. macrolactamization
44%
FK-506
4
OOMe
O
MCPBA, CH2Cl2;CH2C(OCH3)CH3
70%55%
O OO
Me Me
O
MeO O
O
Me Me
OTBSO
Me
vinyl bromide 1 t-BuLi, -78 °C
81%, dr 2:1
OMeTBDPSO
MeOH
MeOOO
Me Me
OTBS
OH
Me
OH
Li
O
OH
BF3•Et2O
OMeTBDPSO
MeO
MeOOO
Me Me
O
O
NBoc
1. DCC, DMAP,2. TBAF3. Dess-Martin Ox.
72%
OO
HO1. TBDPSCl, imh2. MeOH, NaHCO33. MeOTf, 2,6-ditBuPyr
CO2MeMeO
TBDPSO
1. LiAlH42. Swern Ox.3. NaH, N2CHP(O)(OMe)24. n-BuLi, MeI
MeO
TBDPSO
Me
MeO
TBDPSO
Me Br66%
Cp2Zr(H)ClNBS
83%88%1
OMe
OMe
OH OH
1. TrCl, pyr.; NaH, MeI2. Dess-Martin Ox
81%
OMe
OMe
OMe O
1. 3, t-BuLi; MgBr22. NaH, MeI3. aq. HOAc, 80 °C
58%O
MeOH
OMe OMe
TMS
Me
IMe TMS3
2
OMe
OMe OMe
H
Me
1. Ph3P=CHCO2Et2. DIBAL-H3. Sharpless Epox.4. TBAF
64%
OH
OH
1. Me3Al, CP2ZrCl2; I22. TBSCl, DMAP, imh
81%O
Me
OMe OMe Me
OTBSOTBS
IMe
1. t-BuLi; C4H9CCCu•2HMPT; 2, TMSCl; aq. HCl2. TBAF
50%
BocNHO2C
MeO
TBDPSO
Me O
Me
OO O
MeMe
O
ONBoc
Me
Me
OMe
OOMe
Me
HO
HO4
FK-506J. Org. Chem. 1996, 57, 5071 (total synthesis)Tetrahedron 1997, 53, 13257 (full paper of total synthesis)Tetrahedron 1997, 53, 13221 (construction of the C16-C34 fragment)J. Org. Chem. 1992, 57, 5071 (synthesis of the 9,10-acetonide)J. Org. Chem. 1990, 55, 2284 (synthesis of the right side of FK-506)Tet. Lett. 1989, 30, 919 (preparation of the C1-C15 fragment)
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