TY - JOUR
T1 - The total synthesis of rifamycin W
AU - Nakata, Masaya
AU - Akiyama, Nobutake
AU - Kamata, Jun ichi
AU - Kojima, Kyoko
AU - Masuda, Hirokazu
AU - Kinoshita, Mitsuhiro
AU - Tatsuta, Kuniaki
N1 - Funding Information:
Preparation of rifamycin W (1). A mixture of 47 (11.3m g, 0.0111m mol), NaHC03 (6.6 mg, 0.0786m mol), and sodium dithionite (3.9 mg, 0.0224m mol) in 1:l (v/v) DMFH20 (0.45m l) was stirred at 110°C for 10 min. The reaction mixture was poured into saturated aqueous NmCl. Solid NH&I was added to adjust pH to 4 and the mixture was extractedw ith ethyl acetate. The extractsw ere washed with saturateda queousNaCl, dried, and concentratedt o afford the crude 48 (11.0m g, 100%)a s a brown syrup [ Rf = 0.32( 2:l hexane-acetone)l;H NMR 8 (CHCj3=7.26) -0.26 and -0.13 (each 3Hx1.0/2.2, each s, SiMe2), -0.02 and -0.01 (each 3Hx1.2/2.2, each s, SiMe2), 0.69 (9Hx1.0/2.2,s , t-Bu), 0.82 (9Hx1.2/2.2,s , t-Bu), 1.97a nd 1.99( each3 H, eachb r s, H-13 and 15-M& 2.41( 3Hx1.0/2.2,s , ArMe), 2.44( 3Hx1.2/2.2,s , ArMe), 3.49,3.52,3.61,3.61,3.67,3.67,3.67a,n d 3.70 (total 12H, each s, 4xOMe), 4.80 - 5.05 (4H, m, OCH20), 6.29 (lHx1.012.2, s, H-3), and 6.30 (lHx1.2/2.2, s, H-3)]. To a solution of the above crude 48 (11.0m g) in dry toluene (8.51m l) were added diisopropylethylamine (0.0223m l, 0.125 mmol) and bis(2-oxc&oxazolidinyl)phosphinic chloride38 (13.0 mg, 0.0511m mol) at 25°C. After 3 h at 85”C, the reaction mixture was washed with saturated aqueous NaHC03 and NaCl solutions. The aqueous layer was extracted with ethyl acetatea nd the combined organic layers were dried and concentratedt o afford the crude 49 (10.8m g, 100%)a s a brown syrup [Rf = 0.43( 3:l hexane-acetone)].T o a vigorously stirred mixture of the above 49 (10.8m g), AgO (6.4 mg, 0.052m mol) in dioxane (1.1 ml) was added 1N aqueous HN03 (0.0512m l, 0.0512m mol) at 25°C. After 1 h at 25T, the reaction mixture was poured into 1:l (v/v) mixture of saturated aqueous NaCl and NaHCO3 and extractedw ith ethyl acetate.T he extracts were dried and concentrated to afford crude yellow foam (10.4 mg). This sample was dissolved in 1:l (v/v) 1N aqueous HCl-THF (0.3 ml). After 2 d at 25T, the reaction mixture was diluted ethyl acetatea nd washed with saturated aqueous NaCl, dried, and concentrated. The residue was purified by HPTLC (Merck Art 5628,1 0 cm x 10 cm) with 3:l chloroform-MeOH to afford rifamycin W (1) (2.2 mg, 30% from 47): Rf = 0.52 (31 chloroform-MeOH); UV (H20) Lmax nm (log E) 245 (4.41) and 350 (3.81); IR (KBr) 3427, 1636,1 605, 1545,a nd 1492 cm-l; lH NMR (CD30D) 6 0.44 (3H, d, 22-Me, J=7.OHz),0 .71 (3H, d, 24-or 26Me, J=7.OHz),0 .91 (3H, d, 20-Me, J=7.OHz),1 .05( 3H, d, 24 or 26Me, J=7.0Hz),1 .25-1.45( lH, m, H-22), 1.75-1.90( 2H, m, H-24 and 26),1 .99( 3H, s, ArMe), 2.04( 3H, d, Me-13, J=O.gHz),2 .08( 3H, br s, X-Me), 2.25-2.40( lH, m, H-20), 2.55-2.675( lH, m, H-28), 3.45( lH, dd, H-25, J=2.0a nd 10.2Hz),3 .56( lH, dd, one of CH20H, J=7.4 and 11.2Hz), 3.61 (lH, dd, one of CH20H, J=6.4 and 11.2Hz), 3.99 (lH, dd, H-23, J22,23=9.8a nd J23,24<1.OHz), 4.05 (lH, dd, H-21, J20,21=10.0 and J21,22<1.OHz), 4.29 (lH, s, H-27, J26,27=J27,2g=OHz)6, .09 (lH, dd, H-19, Jlg,l9=16.0 and Jl9,20=6.8Hz), 6.23 (lH, d, H-17, Jl7,lg=ll.OHz), 6.52 (lH, br d, H-29, J2g,29=10.0a nd J29,Me_l3=0.8HZ), 6.54 (lH, dd, H-18, J17,lg=ll.O and J1g,l9=16.OHz)a, nd 7.37( lH, s, H-3). The synthetic sample of rifamycin W (1) was identical spectroscopically and chromatographicallyw ith natural rifamycin ~.6b/l8 Acknowledgment: We are grateful to the Institute of Microbial Chemistry for the generous support of our program. Financial support by the Ministry of Education, Science and Culture (Grant-in-Aid for Scientific Reseach)i s gratefully acknowledged.
PY - 1990
Y1 - 1990
N2 - The first total synthesis of rifamycin W (1) has been accomplished by coupling two segments of the aliphatic ansa-chain 40 and the aromatic chromophore 12. The totally enantiospecific sequence elucidates the configurations of the C28 position and the C12 - C29 double bond to be R and E, respectively.
AB - The first total synthesis of rifamycin W (1) has been accomplished by coupling two segments of the aliphatic ansa-chain 40 and the aromatic chromophore 12. The totally enantiospecific sequence elucidates the configurations of the C28 position and the C12 - C29 double bond to be R and E, respectively.
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U2 - 10.1016/S0040-4020(01)85586-1
DO - 10.1016/S0040-4020(01)85586-1
M3 - Article
AN - SCOPUS:0024987705
VL - 46
SP - 4629
EP - 4652
JO - Tetrahedron
JF - Tetrahedron
SN - 0040-4020
IS - 13-14
ER -