Four Papers on the Chemical Nature of Vitamin K
1939–1941. First Edition. Doisy received the Nobel Prize in Physiology or Medicine in 1943 for determining the chemical nature of vitamin K, the fat-soluble compound whose absence from the diet produces uncontrolled hemorrhage by impairing the blood's ability to clot. The vitamin had been identified as a distinct nutritional factor by Henrik Dam in 1935, but its chemical identity remained unknown until Doisy's laboratory at Saint Louis University isolated, characterized, and synthesized both of its naturally occurring forms. The four papers gathered here trace that achievement in compact form: two brief 1939 communications establishing the antihemorrhagic activity of synthetic quinones and proposing a practical standard for their assay; a 1940 note summarizing the structural determinations of vitamins K and K and reporting the preparation of water-soluble derivatives suitable for clinical use; and a major 1941 review consolidating the chemistry, biological testing, and structural elucidation of the entire vitamin K group. Together they document not merely the identification of a vitamin, but the rapid conversion of a nutritional observation into a coherent biochemical program linking isolation, synthesis, standardization, and therapeutic application. Vitamin K is today administered to virtually every newborn in the developed world to prevent fatal bleeding, and remains essential to the management of clotting disorders and anticoagulant therapy. Item #1292
[Thayer, S. A., L. C. Cheney, S. B. Binkley, D. W. MacCorquodale, and E. A. Doisy]. "Vitamin K Activity of Some Quinones; reprinted from the Journal of the American Chemical Society, Vol. 61, p. 1932." Easton, PA: American Chemical Society, 1939. Offprint, single leaf, trimmed 8vo (186 × 199mm). Trimmed at the bottom, old tape offsetting to the margin, else very good. A brief communication reporting the vitamin K activity of an extensive series of quinone derivatives assayed against natural vitamins K and K as standards. Written in direct response to Almquist and Klose's claim that phthiocol was the simplest active member of the antihemorrhagic series, the paper demonstrates that all derivatives of 1,4-naphthoquinone — with the exception of 2-allyl-1,4-naphthoquinone — show measurable vitamin K activity, with 2-methyl-1,4-naphthoquinone the most potent at 10 units per milligram, though markedly less active than the natural vitamins. The activity of two dihydro-1,4-naphthoquinone diacetates is attributed to gastrointestinal hydrolysis, and the paper cross-references the concurrent structural determination of vitamin K published in the same journal volume.
[Thayer, S. A., S. B. Binkley, D. W. MacCorquodale, E. A. Doisy, A. D. Emmett, Raymond A. Brown, and Orson D. Bird]. "Vitamin K Potencies of Synthetic Compounds; reprinted from the Journal of the American Chemical Society, Vol. 61, p. 2563, 1939." Easton, PA: American Chemical Society, 1939. Offprint, single leaf, trimmed 8vo (192 × 200mm). Trimmed at the bottom, old tape offsetting to the margin, else very good. A follow-up communication conducted in collaboration with the Research Laboratories of Parke, Davis and Company, supplementing the quinone activity survey of the preceding paper. The principal finding is that 1,4-dihydroxy-2-methylnaphthalene, readily prepared by reduction of 2-methyl-1,4-naphthoquinone, possesses a potency of approximately 1,000 Thayer-Doisy units per milligram and has the clinical advantage of solubility in dilute alkali, making it suitable for intravenous administration in patients unable to absorb oral preparations. The paper concludes with the proposal that 2-methyl-1,4-naphthoquinone be adopted as a universal assay standard, defined as the specific activity of one microgram of the pure compound in League of Nations committee units — a standardization recommendation with immediate practical significance for the clinical deployment of vitamin K therapy.
[Doisy, E. A., S. B. Binkley, S. A. Thayer, E. W. McKee, and D. Richert]. "Antihemorrhagic Compounds; reprinted from Science, Vol. 91, No. 2366, p. 421, May 3, 1940." Washington, D.C.: American Association for the Advancement of Science, 1940. Offprint, single leaf, 8vo (230 × 153mm). Soft creases, else fine. A brief communication presented before the National Academy of Sciences, summarizing the structural program following the isolation of both natural antihemorrhagic compounds. The structure of vitamin K was deduced from degradation experiments and confirmed by synthesis; vitamin K , while sharing the 2-methyl-1,4-naphthoquinone core, bears a thirty-carbon hydrocarbon substituent at the 3-position in place of the phytyl chain of K . The water insolubility of both natural compounds limiting their suitability for parenteral use, the authors report the preparation of several water-soluble synthetic derivatives and their intravenous administration to vitamin K-deficient chicks, with activity assessed by restoration of prothrombin time to normal.
[Doisy, E. A., S. B. Binkley, and S. A. Thayer]. "Vitamin K; reprinted from Chemical Reviews, Vol. 28, No. 3, pp. 477–517, 1941." Washington, D.C.: American Chemical Society, 1941. Offprint, 8vo (254 × 175mm), pp. 41, [1]. Printed wrappers, staple-bound, rubbing, toning, and light soiling, else very good. A comprehensive review providing an authoritative account of the vitamin K field at the point of its maturity. The paper moves systematically from Dam's original identification of an unknown fat-soluble antihemorrhagic factor in 1935 through the isolation, structural determination, and synthesis of vitamins K and K , before turning to a detailed structure-activity survey of synthetic quinone derivatives. The isolation sections describe the fractionation of alfalfa and putrefied fish meal that yielded K and K respectively; the structural sections document the deduction of the shared 2-methyl-1,4-naphthoquinone core and the characterization of the differing substituents at the 3-position; and an extensive tabulation of antihemorrhagic potencies, assayed by prothrombin time in deficient chicks, reflects the laboratory's concurrent program of therapeutic development. The contributions of Dam, Almquist, and other competing laboratories are assessed alongside those of Doisy's group, making the review one of the principal contemporary accounts of the work for which Doisy received the Nobel Prize.
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