Display Settings:

Items per page

Results: 11

1.
Fig. 2.

Fig. 2. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

Retrosynthetic analysis of macrolactone and macrocarbocyclic cytochalasins.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
2.
Fig. 1.

Fig. 1. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

Structures of macrolactone and macrocarbocyclic cytochalasins.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
3.
Fig. 4.

Fig. 4. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

Control of facial selectivity in diene addition by allylic 1,3-strain considerations (40–42).

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
4.
Fig. 3.

Fig. 3. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

The proposed biosynthetic route to the cytochalasins involves the “natural” Diels–Alder disconnection shown (28). Previous syntheses of the cytochalasins have used a similar Diels–Alder disconnection (1–9). Retrosynthetic modification of 6 permits the implementation of an alternative Diels–Alder disconnection.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
5.
Scheme 2.

Scheme 2. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

Reaction conditions. a: Trifluoroacetic acid, CH2Cl2,0°C. b: [Bis(trifluoroacetoxy)iodo]benzene, 2,6-lutidine, 4 Å MS, CH2Cl2, 23°C, 90% (two steps). c: 1,3-Diaminopropane, CF3CH2OH, Et2O, 23°C; Et2O–pH 7 buffer. d: KOH, I2, CH3OH, 23°C, 96% (two steps). e: Dimethyldioxirane, acetone, 23°C, 100%. f: Trifluoroacetic acid, CH2Cl2, 0°C. g: [Bis(trifluoroacetoxy)iodo]benzene, 4 Å MS, CH2Cl2, 23°C, 92% (two steps). h: Ethylenediamine, tert-amyl alcohol, 23°C, 96%.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
6.
Scheme 4.

Scheme 4. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

Reaction conditions. a: Lithium diisopropylamide, LiCl, THF, -78°C → 23°C; 2-benzyloxy-1-iodoethane, 0°C, 94%. b: LiH2NBH3, THF, 23°C, 88%. c: PPh3,I2, imidazole, CH2Cl2,23°C, 89%. d: 8, Lithium diisopropylamide, LiCl, THF, -78°C → 23°C; 27,23°C. e: LiH2NBH3, THF, 23°C, 91% (two steps). f: tert-Butyldiphenylsilyl chloride (TBDPSCl), Et3N, dimethylaminopyridine, CH2Cl2, 23°C, 89%. g: H2, Pd(OH)2/C, EtOAc, 23°C. h: 1-Phenyl-1H-tetrazole-5-thiol, PPh3, diethyl azodicarboxylate (DEAD), THF, 23°C, 86% (two steps). i: m-Chloroperbenzoic acid, NaHCO3, CH2Cl2, 23°C, 97%.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
7.
Scheme 6.

Scheme 6. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

Reaction conditions. a: Dimethyldioxirane, acetone, 23°C, 95%. b: Dess–Martin periodinane, NaHCO3,CH2Cl2,23°C. c: 10, KHMDS, THF, -78°C; 9, -100°C → -40°C, 86% (two steps). d: (CH3O)2POCH2Li, THF, -78°C → 23°C. e: TBAF, AcOH, THF, 23°C, 81% (two steps). f: Dess–Martin periodinane, NaHCO3,CH2Cl2,23°C. g: NaOCH2CF3,CF3CH2OH, DME, 80°C, 52% (two steps, 5:1 mixture of diastereomers). h: CeCl3·7H2O, NaBH4, THF–CH3OH, -40°C. i: Ac2O, pyridine, 23°C, 86% (two steps). j: MgSO4, benzene, 60°C, 77%.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
8.
Scheme 1.

Scheme 1. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

Synthesis of a key tricyclic precursor (6) to macrolactone and macrocarbocyclic cytochalasins. Reaction conditions. a: Diethyl 3-oxo-2-butylphosphonate (14), Ba(OH)2, tetrahydrofuran (THF)–H2O, 23°C, 87%. b: 2,3-Dichloro-5,6-dicyanobenzoquinone, CH2Cl2–pH 7 buffer, 23°C, 86%. c: tert-Butyldimethylsilyl trifluoromethanesulfonate, 2,6-lutidine, CH2Cl2, -78°C → 23°C, 99%. d: CH3OH, 23°C, 98%. e: m-Xylene, 150°C, 77%. f: H2, 10% Pd/C, BOC2O, Et3N, EtOH, 23°C, 96%. g: TBAF, AcOH, THF, 0°C. h: KHMDS, THF, -78°C; 2-[N,N-bis(trifluoromethylsulfonyl)amino]-5-chloropyridine, 93% (two steps). i: (CH3)2CuLi, THF, -78°C → 0°C, 95%.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
9.
Scheme 5.

Scheme 5. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

Reaction conditions. a: (1S,2S)-1,2-cyclohexanediamino-N,N′-bis(3,5-di-tert-butylsalicylidene)cobalt(II), AcOH, H2O (0.45 eq), 0°C → 23°C, 41% (45% theoretical yield). b: tert-Butyldimethylsilyl trifluoromethanesulfonate, Et3N, CH2Cl2,0°C → 23°C. c: H2,Pd/C, EtOAc, 23°C, 79% (two steps). d: PPh3, I2, imidazole, CH2Cl2, 23°C, 86%. e: Dess–Martin periodinane, CH2Cl2, 23°C. f: TsNHNH2, THF, 23°C, 94% (two steps). g: tert-Butyldimethylsilyl trifluoromethanesulfonate, Et3N, THF, -78°C. h: 32, tert-BuLi, Et2O, -78°C; 34, THF; AcOH, CF3CH2OH, -78°C → 23°C, 90% (two steps). i: H2, Pd/C, EtOAc, 23°C, 87%. j: 1-Phenyl-1H-tetrazole-5-thiol, PPh3, diisopropyl azodicarboxylate (DIAD), THF, 23°C, 90%. k: m-Chloroperbenzoic acid, NaHCO3, CH2Cl2, 23°C, 84%.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
10.
Scheme 7.

Scheme 7. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

Reaction conditions. a: Dess–Martin periodinane, NaHCO3, CH2Cl2,23°C. b: 5, KHMDS, THF, -78°C; 4, -100°C → -40°C, 60% (two steps). c: Lithium bis(trimethylsilyl)amide, THF, -78°C; BOC2O, -78°C → -40°C, 80%. d: KHMDS, THF, -78°C; trans-2-(phenylsulfonyl)-3-phenyloxaziridine, -100°C → -78°C, 85%. e: Diethylphosphonoacetic acid, 1,3-dicyclohexylcarbodiimide, CH2Cl2, 23°C, 81%. f: HF·pyridine, THF, -20°C, 69%. g: Dess–Martin periodinane, NaHCO3, CH2Cl2, 23°C. h: NaOCH2CF3, CF3CH2OH, DME, 23°C, 65% (two steps). i: Mg(OCH3)2,CH3OH, 23°C, 95%. j: TBAF, THF, 23°C, 96%. k: MgSO4, benzene, 70°C, 66%.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.
11.
Scheme 3.

Scheme 3. From: An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B.

In theory, simple hydrolysis of the imine intermediate 19 should free the amino group for the desired intramolecular attack on the γ-lactone ring (see Scheme 3, 1923). We found that although 19 was, in fact, transformed to lactam 23 after heating in aqueous acetic acid, the product and starting material were of equal energies (1:1 ratio at equilibrium). Other hydrolysis conditions were complicated by competing deformylation of 23, a finding that was used later to advantage in the synthesis of 1. The problem was solved by devising a nonhydrolytic opening of the imine group of 19 using 1,3-diaminopropane as the nucleophile, forming the lactam 25 via the amino lactone 24 (not observed). Mild hydrolysis of 25 (ether–pH 7 aqueous sodium phosphate buffer solution) then provided the desired aldehyde 23 in quantitative yield. Without purification, aldehyde 23 was directly transformed to the methyl ester 20 by treatment with potassium hydroxide and iodine in methanol (46) (see Scheme 2). The yield of 20 from the imine 19 was 96%.

Andrew M. Haidle, et al. Proc Natl Acad Sci U S A. 2004 August 17;101(33):12048-12053.

Display Settings:

Items per page

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Write to the Help Desk