The complete nucleotide sequence of the hemagglutinin (HA) gene of the human type B influenza virus B/Singapore/222/79 is presented. Comparison with the only other known sequence of a B hemagglutinin (B/Lee/40) shows that antigenic drift in type B HA genes is essentially the same as already observed within the influenza A H3 subtype, i.e., an accumulation of point mutations. The main difference is that the apparent evolution is significantly slower, most likely due to the cumulative effect of a lower occurrence in the population (slower evolution) and/or less immunological pressure. There is a striking cluster of changes at positions 127 until 137 of the HA1 subunit which may represent one of the antigenic sites of the molecule.
Various ways to substitute the nitrogen atom of isoxazolin-5-one are described. The properties of synthetic 2-substituted 3.4-unsubstituted isoxazolin-5-ones are compared with the natural compounds. The structure of the natural 2-(2-cyanoethyl)-3-isoxazolin-5-one has been proven by establishing its identity with the synthetic compound.A NUMBER of 2-substituted 3,4-unsubstituted isoxazolin-5-ones have been isolated from Pisum sativum and Lathyrus odoratus ~eedlings.l-~ They are the only known natural compounds with an isoxalin-&one ring. The confirmation of their chemical structure by synthesis was therefore desirable. Isoxazolin-5-one was first mentioned as a reaction product arising from nucleic acids by treatment with hydro~ylamine.~*~ Its synthesis and properties were described by De Sarlo? and on alkylation with diazomethane it gave 2-methyl-3isoxazolin-&one. This paper reports other ways to alkylate the nitrogen atom of isoxazolin-5-0ne.~
RESULTS AND DISCUSSIOKThe isoxazolin-5-one anion (1) was alkylated by ally1 bromides, dialkyl sulphates and toluene-$-sulphonates. Cyanoethylation of isoxazolin-5-one (1) was achieved with acrylonitrile. Only strong alkylating agents could substitute the isoxazolin-5-one anion (1). Dialkyl sulphates react readily, while toluene-p-sulphonates react rather slowly. Alkyl iodides, ethyl chloroacetate, and
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