ABSTRACT. It has been often found that the provisionized Japanese monkeys here limb-malformed babies since 1955 in Japan. We reported that some organochlorin pesticide residues might have related to the cause of the malformation of limbs. It was found that the tissues of the dead Japanese monkeys were contaminated with Heptachlor epoxide, Dieldrin, BHC, DDT, and Chlordane isomers. The concentrations of Heptachlor epoxide in the malformed monkeys were significantly higher (kidney, p<0.05) than those in the normal monkeys. The levels of Heptachlor epoxide (kidney) and Dieldrin (liver) in the adult female monkeys who had borne malformed babies were also significantly higher (p<0.05) than those in the adult females who had not.Relation of the Congenital Limb-malformation in the Japanese Monkeys and Organochlorin Pesticides

1,6,10,15-Tetramethyl-7,9,15,17-cyclooctadecatetraene-2,4,11,13-tetrayne-1,6-diol (VII), a 18-membered cyclic glycol, was synthesized by a stepwise reaction sequence starting from 3-methyl-2-penten-4-ynal (III). Treatment of the cyclic glycol (VII) with stannous chloride dihydrate in concentrated hydrochloric acid yielded tetramethyltetrakisdehydro[18]annulene (VIII). Examination of the NMR spectra clearly indicates that the tetrakisdehydro[18]annulene (VIII) containing formal diacetylene and hexapentaene units sustains a strong diamagnetic ring current and has a high conformational stability.

Reduction of methyl hydrogen di-O-acetyl-dextro-tartrate (I) with sodium borohydride in water afforded l-threono-γ-lactone (II). l-Threose (IV) was obtained on treatment of the γ-lactone (II) with an excess of disiamylborane. Reduction of ester chloride of di-O-acetyl-dextro-tartaric acid (VI) with tri-n-butyltin hydride yielded methyl di-O-acetyl-l-threuronate (VII). Attempts to reduce 2-deoxy-pentarate ester (X) derived from ester chloride (VI) via diazoketone (VIII) with sodium borohydride to give 2-deoxy-threo-pentono-γ-lactone (XI) gave unsatisfactory results. Formation of methyl l-threo-2,3-di-O-acetyl-5-chloro-5-deoxy-4-C-hydroxymethyl-4,4′-anhydropentonate (IX) in addition to diazoketone (VIII) was observed when ester chloride (VI) was treated with an excess of diazomethane. On the basis of the observed (−)-Cotton effect in the 290 nm region of ORD and CD spectra of l-threose (IV) and d-erythrose, possibility of the presence of an open chain non-hydrated alde-hyde-form of aldotetrose in water was discussed.

5-Bromo-2,5-dideoxy-threo-pentono-γ-lactone (III) could be obtained stereoselectively from 3-hydroxy-4-pentenoic acid (I) by the reaction with N-bromosuccinimide in water. On successive treatment with an aqueous potassium hydroxide and an acid type cation exchange resin, bromolactone (III) gave stereoselectively 2-deoxy-erythro-pentono-γ-lactone (IV). Reduction of IV by means of bis(1,2-dimethylpropyl)borane afforded 2-deoxy-erythro-pentose (V). 3-Hydroxy-4-pentenoic acid (I) could be optically resolved. The (+)-acid yielded 2-deoxy-d-erythro-pentose (d-V) and the (−)-acid could be converted to 2-deoxy-l-erythro-pentose (l-V). 2,5-Dideoxy-threo-pentose (VIII) and 5-bromo-2,5-dideoxy-threo-pentose (IX) were obtained from bromo-lactone (III). Diethyl mercaptal of IX gave azido-compound (XI) in a low yield by the reaction with sodium azide. The conformation of γ-lactones (III, IV, and VII) and the mechanistic aspects of stereoselective reactions are discussed.

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