Structure-lnsecticidal Activity Relationship of Five-Membered Cyclic Phosphoramidates Derived from Amino Acids

Morifusa Eto, Akinpri Hirashima, Shinkichi Tawata, Kohei Oshima

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11 Citations (Scopus)

Abstract

About seventy 1,3,2-oxazaphospholidine derivatives were synthesized from ar-amino acids according to the reaction scheme 2 or 3 and their insecticidal activity against houseflies was examined in comparison with some related heterocyclic phosphorus compounds. The insecticidal activity of these cyclic phosphorus compounds was influenced by several factors as follows: 1) The ring size. Five-membered. ring was necessitated for the biological activities (Table 7). 2) 4-Alkyl group or amino acid used. L-Leucine and L-valine gave highly insecticidal derivatives (Tables 1 and 2). 3) The configuration of the carbon atom at 4-position. D-Leu-cine gave the less active derivatives than L-leueine (Table 1). 4) The exo-cyclic substituent on the phosphorus atom. The smaller the alkyl group, the higher the insecticidal activity. 5) The position of an alkyl substituent. The 4-alkyl derivatives were better than the 3- or 5-alkyl derivatives (Table 3). Condensation of a benzene ring to the five-membered ring caused a great decrease in insecticidal activity (Table 5). 6) The hetero atoms. Replacement of the oxygen atom in the hetero ring by a sulfur atom improved the insecticidal activity (Table 4). Thus, (45)-4-isobutyl-2-methoxy-l, 3,2-oxazaphospholidine 2-sulfide and the 4-isopropyl homolog were most promising as insecticides.They were particularly effective to control the organophosphate-resistant strains of houseflies (Table 6). Several 2-alkoxy-l, 3, 2-oxazaphospholidine 2-oxides inhibited acetylcholinesterase (AChE). The activity was also influenced by the exo-cyclic phosphorus substituent (Table 7). Oxazaphospholidine 2-sulfides were stabler than dioxaphosphole sulfides particularly under alkaline conditions, whereas the oxazaphospholidine was more active chemically rather than the dioxaphosphole in the 2-oxide analogs (Table 8). The distance between the phosphorus atom and the hydrophobic branched alkyl-center is about 4.8 A in the leucine-derived cyclic phosphoramidate. This is almost the same as the hypothetical distance between the esteratic site and the binding site of AChE. A hypothetical mechanism suggesting the importance of 4-alkyl group for AChE inhibition was proposed (Fig. 1).

Original languageEnglish
Pages (from-to)705-711
Number of pages7
JournalNIPPON KAGAKU KAISHI
Volume1981
Issue number5
DOIs
Publication statusPublished - Jan 1 1981

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

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