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HO OH
Me
Me
OO
ClMe
Me
Me
CEM 85201-25-20
KONIKA
1Angew. Chem. Int. Ed. 2019, 58, 2490
In 2012, Fenical and Moore isolateda novel class of meroterpenoidsfrom actinomycetes strain (CNH-189) in California
Merochlorin A belongs tomeroterpenoid family
Isolated from Streptomyces sp. Displays antibiotic activity against
C. dificile and S. aureus Interesting structure Absolute configuration unknown First total asymmetric synthesis
HO OH
Me
Me
OO
ClMe
Me
MeBicyclo[3.2.1]
resorcinol
2Angew. Chem. Int. Ed. 2019, 58, 2490
OAc
Au(I)OAc
LAu
H H
OAc
H H
3G. LemiHre,V.Gandon, K. Cariou, A. Hours,T.Fukuyama, A.L. Dhimane,L.Fensterbank, M. Malacria, J. Am. Chem. Soc. 2009, 131,2993–3006.
OAc
MeOBz
O
H
Au(I)-catalysis
Me
O
H
OH
OBz
OBz
O
H
H
Me
OAc AcO
Me
OBz
HONazarov
cyclization
Au(I) 1,3-acyloxymigration
Au(I)
Au(I) Aldol reaction
pentalene
4Angew. Chem. Int. Ed. 2019, 58, 2490
HO OH
Me
Me
OO
ClMe
Me
Me
Diels-Alder &aromatization
TransannularAldol reaction
O
Cl
CHO
Me
MeHMe
MeMe
Me
O
H
OH
OBzC=O olefination
conjugate addition
enolate chlorination
pentalene
5Angew. Chem. Int. Ed. 2019, 58, 2490
OAc
MeOBz
O
H
Au(I)-catalysis
Me
O
H
OH
OBz
OBz
O
H
H
Me
OAc AcO
Me
OBz
HO
Nazarovcyclization
Au(I)1,3-acyloxymigration
Au(I)
Au(I) Aldol reaction
6Angew. Chem. Int. Ed. 2019, 58, 2490
OAc
MeOBz
O
H
Ph3PBr
59.3 mmol
LiBr (2.0 equiv)
THF, r.t., 10 min
PhLi (1.0 equiv)
Et2O, -78°C to r.t., 45 min
OTBSOHC
(1.0 equiv)THF, -78°C, 10 min
PhLi (1.1 equiv)
Et2O, -78°C to r.t., 1 h
II
(1.2 equiv)THF, -78°C to r.t., 1.5 h
I
OTBS
71%, E/Z= 10:1
7Angew. Chem. Int. Ed. 2019, 58, 2490
OAc
MeOBz
O
H
I
OTBS
28.10 mmol
Me
OAc(1.1 equiv)
Et3N-THF, r.t., 2h
PdCl2(PPh3)2 (5 mol%)CuI (10 mol%)
OTBS
Me
OAc
83%
OTBS
Me
OAc
20.82 mmol
9-BBN (1.8 equiv)
THF, 0°C to r.t., 2h
NaBO3.4H2O( 30 equiv)
THF- H2O, 0°C to r.t., 4 h
OTBS
Me
OAcOH
84%
BH
9-BBNexists as dimer
8Angew. Chem. Int. Ed. 2019, 58, 2490
OTBS
Me
OAcOH
17.55 mmol
BzCl (1.2 equiv)pyridine ( 2.0 equiv)
CH2Cl2, r.t., 4 hOTBS
Me
OAcOBz
96%
OTBS
Me
OAcOBz
OH
Me
OAcOBz
17.02 mmol
TBAF (1.5 equiv)
THF, r.t., 2 h
93%
9Angew. Chem. Int. Ed. 2019, 58, 2490
N+F
-
TBAF
OH
Me
OAcOBz
O
Me
OAcOBz
oxalyl chloride (1.2 equiv)
14.01 mmol
DMSO (2.4 equiv)
CH2Cl2, -78°C,30 min
Et3N (5.0 equiv)
CH2Cl2, -78°C to r.t., 1 h
90%
10Angew. Chem. Int. Ed. 2019, 58, 2490
O
OCl
Cl
oxalyl chloride
O
Me
OAcOBz
13.22 mmol
Echavarren's catalyst (5 mol%)THF, 0.2 vol% H2O, -10°C, 16 h
Me
O
H
OH
OBz
Me
O
H
OAc
OBz
73%,dr=3:1 15%
Pt-But-Bu
Au NCMeSbF6
Echavarren’s catalyst
11Angew. Chem. Int. Ed. 2019, 58, 2490
Me
O
H
OH
OBz
Me
O
H
OBz
11.45 mmol
Tf2O (1.1 equiv)2,6-lutidine (5.0 equiv)
CH2Cl2, -78°C to 0°C, 1 h
DBU (10 equiv)
CH2Cl2,0°Cto r.t., 1 h
65%
Me
O
H
OBz
Me
O
H
OBz
O
PdCl2 (10 mol%)
CuCl ( 1.0 equiv)O2
(1 atm)
DMF-H2O (7:1),r.t., 96 h
7.76 mmol 85%
12Angew. Chem. Int. Ed. 2019, 58, 2490
N
2,6 lutidine
Me
O
H
OBz
OLaCl3.2LiCl (5.0 equiv)
4.48 mmol
THF, r.t., 1 h
MeMgBr
(2.0 equiv)THF, -78°C to -40°C, 30 min
Me
O
H
OBz
OH
Me
86%
Me
O
H
OBz
OH
Me
3.84 mmol
BF3.OEt2 (1.5 equiv)Et3SiH (50.0 equiv)
CH2Cl2, 0°C to r.t., 3 h
Me
O
H
OBz
Me
Me
61%
13Angew. Chem. Int. Ed. 2019, 58, 2490
Me
O
H
OBz
Me
Me
Me
MeI
1.5 equivEt2O, -78°C, 20 min
t-BuLi (3.0 equiv)LiCu(CN)(2-thiofurenyl)
(1.5 equiv)Et2O, -78°C, 1 h
(1.80 mmol)BF3.OEt2 (2.0 equiv)
THF, -72°C, 18 h
O
H
OBz
Me
Me
MeMe
Me
87%
O
H
OBz
Me
Me
MeMe
Me
O
H
OBz
Me
Me
MeMe
MeCl
1.54 mmol
CH2Cl2,0°C to r.t., 30 min
Et3N (5.0 equiv)TMSOTf (3.0 equiv) CBMG (1.2 equiv)
CH2Cl2, r.t., 30 min
98% dr=2:1
NH
NH
NCl
CO2MeMeO2C
CBMG
14Angew. Chem. Int. Ed. 2019, 58, 2490
O
H
OBz
Me
Me
MeMe
MeCl
O
H
OH
Me
Me
MeMe
MeCl
1.51 mmol
K2CO3 (3.0 equiv)
MeOH-THF (1:1), r.t., 1 h
96%
O
H
OH
Me
Me
MeMe
MeCl
HMe
Me
MeMe
MeCl
O
O
1.30 mmol
PDC (4.0 equiv)
DMF, r.t., 3 hNaOAc (5.0 equiv)
Ac2O, 140°C, 15 min
68%
15Angew. Chem. Int. Ed. 2019, 58, 2490
HMe
Me
MeMe
MeCl
O
O
0.31mmol
DIBAL-H (1.3 equiv)
toluene,-78°C to 0°C, 2 h Me
Me
HOO
ClMe
Me
Me
85%
Me
Me
HOO
ClMe
Me
Me
Me
Me
OO
ClMe
Me
Me
0.06 mmol
PCC (20 equiv)celite
CH2Cl2, r.t., 24 h
94%
16Angew. Chem. Int. Ed. 2019, 58, 2490
Me
Me
OO
ClMe
Me
Me
0.057 mmol
LDA(1.2 equiv)THF, -78°C, 15 min
PhS Cl
N t-Bu
(1.1 equiv)THF, -78°C, 15 min Me
Me
OO
ClMe
Me
Me
MeO
OMe
OTMS
Brassard’s diene
Me
Me
OO
ClMe
Me
MeEt3N ( 6.0 equiv)
TMSOTf (3.0 equiv)CH2Cl2, 0°C, 30 min
Pd(OAc)2 (1.5 equiv)
MeCN,r.t., 3 h
48%
MeO OH
Brassard's diene (3.0 equiv)
toluene, 100°C, 1 h
17Angew. Chem. Int. Ed. 2019, 58, 2490
Me
Me
OO
ClMe
Me
Me
MeO OH
Me
Me
OO
ClMe
Me
Me
HO OH
0.017 mmol
LiCl (15.0 equiv)DMF, r.t. to 140C,4 h
70%
Merochlorin A
18Angew. Chem. Int. Ed. 2019, 58, 2490
19G. Mahler,G.Serra, E. Manta, Synth. Commun. 2005, 35,1481– 1492.
Br37 mmol
PPh3 (1.0 equiv)
toluene, 100°C, 24 hPPh3Br
68%
Commercially available$24 per gram
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