Syntheses of hydantocidin and C-2-thioxohydantocidin
2,3-O-Isopropylidene-d-ribono-1,4-lactone was converted to hydantocidin in good yield and C-2-thioxohydantocidin via isothiocyanates 13, 18, or 22.
Introduction
Together with the explosive increase in the world population, deficiency of provisions, environmental destruction and pollution, and global warming have become serious problems. Means for grain production to maintain this large population have come under increased development. One aspect is the use of herbicides. Glyphosate has become one of the most popular herbicides in the world. However, glyphosate-resistant weeds have been reported recently. In addition, proteins produced by grain plants recombinated by a glyphosate-resistant gene are a cause for concern, because of the awareness of the existence of pathogenic proteins.
Hydantocidin produced from Streptomyces hygroscopicus,1 the first naturally occurring spiro-ribofuranose having strong herbicidal activity toward annual, biennial and perennial weeds by action as an adenylosuccinate synthetase inhibitor2., 2.(a), 2.(b), 2.(c), 2.(d) without showing toxicity to microorganisms and animals and without remaining for a long period in the soil, may be used in the near future as a potential herbicide against glyphosate-resistant weeds. However, the high cost of hydantocidin production, whether by fermentation or by total synthesis,3., 3.(a), 3.(b), 3.(c), 3.(d), 3.(e), 3.(f), 3.(g), 3.(h), 3.(i), 3.(j), 3.(k) has made its use as a herbicide impractical. Therefore, economical production of hydantocidin is being sought. At this time, the author has accomplished a fairly good overall yield for hydantocidin, that is, hydantocidin 12 was synthesized in 35.2% overall yield accompanying epi-hydantocidin 12′ in 9.6% overall yield from 2,3-O-isopropylidene-d-ribono-1,4-lactone (1). And also C-2-thioxohydantocidin 24 was synthesized from 1 in 16.5% overall yield via isothiocyanate 22. Therefore, I would like to report the synthetic procedure in detail here.4
Section snippets
Results and discussion
The starting material, 2,3-O-isopropylidene-d-ribono-1,4-lactone (1),5 was converted to 5-O-benzyl ether 2 or 5-O-(4-methoxybenzyl) ether 15 in 95 or 77% yield, respectively, by treatment with benzyl bromide or 4-methoxybenzyl chloride using NaH as a base. Treatment of 2 with CBrCl3 using tris(dimethylamino)phosphine [(Me2N)3P] as a base according to Chapleur's procedure6 gave dichloroolefin 37., 7.(a), 7.(b), 7.(c), 7.(d), 7.(e), 7.(f) in 86% yield. Compound 15 also gave 16 in 95% yield. In
Experimental
Melting points were determined on a Yanagimoto micro melting point apparatus and are uncorrected. Optical rotations were obtained by the use of a JASCO P-1030 polarimeter. 1H NMR spectra were recorded with a JEOL-GSX 400 spectrometer (400 MHz) using TMS as the internal standard, and 13C NMR spectra were recorded at 125 MHz using TMS as the internal standard. IR absorption spectra were determined with an IR A-2 spectrophotometer, and mass spectra were obtained with a JMS-700 mass spectrometer.
Acknowledgments
I would like to thank Dr. Shigeru Mio for helpful advice and discussions.
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