TANOKURA Masaru The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (60136786)
OKUBO Akira The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (20111479)
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¥3,400,000 (Direct Cost : ¥3,400,000)
Fiscal Year 2004 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 2003 : ¥2,300,000 (Direct Cost : ¥2,300,000)
We present two new NMR techniques prepared by modification of HMBC, High Resolution HMBC (HR-HMBC) and BIRD-J resolved HMBC.
1)High Resolution HMBC (HR-HMBC)
In the conventional HMBC spectra, the cross peaks contain information on the long-range J_<CH> splittings and/or J_<HH> splittings. Due to the poor resolution in the F_2 or F_1 dimension, however, it is difficult to measure the long-range J_<CH> couplings directly from HMBC cross peaks.
In order to solve this problem, we have incorporated the J-scaling method into HMBC and developed a new technique, HR-HMBC.
The J-scaling pulse (--nt_1/2-180(H,C)-nt_1/2--) is introduced after the spin evolution period of HMBC. In this pulse sequence, the magnetizations of chemical shift, J_<HH> and J_<CH> coupling constants evolve with t_1, (n+1)t_1 and nt_1, respectively. As a result, the spin coupling constants are amplified by a factor of n for J_<CH> and n+1 for J_<HH> (n=20 to 30).
This modification enables to determine easily long range J_<CH> co
uplings of complicated compounds and will be useful for conformational analysis of non-cyclic systems. Advantages of this method are simple operation, high sensitivity and general applicability.
For stereochemical studies of organic molecules by NMR, it is important to analyze proton-proton spin coupling constants. Natural products such as polyketide often contain the spin system which includes a secondary methyl group (-CH_A-CH_B(CH_3)-CH_C-). In such a spin system, proton H_B splits complicatedly. Thus, it becomes very difficult to obtain spin coupling constants from the multiplet signal of H_B. Analysis of spin coupling pattern of H_B is sometimes essential for stereochemical studies. The new NMR techniques BIRD-J-resolved HMBC and BIRD-HR-HMBC are useful in order to overcome this problem.
We have already reported J-resolved HMBC^<1)> methods to observe long range J_<CH> couplings. By incorporation of the scaling pulse into HMBC, proton-proton spin splittings in the F_1 dimension are magnified by a factor of n (n=20 to 30) making measurement of J_<CH> very easy. In these pulse sequences, 180 pulse is put into BIRD pulse.
The BIRD pulse modulates only protons directly connected to ^<12>C and not protons connected to ^<13>C. In other words, protons connected directly to ^<13>C are decoupled. For example, in a spin system (-CH_A-CH_B(^<13>CH_3)-CH_C-), proton H_B with its adjacent methyl protons being decoupled are coupled only to H_A and H_C in J-resolved HMBC and HR-HMBC spectra. Thus this technique enables easier analysis of the multiplet H_B with complicated splitting pattern. An application of this method to a model compound portmicin is explained. Less