674
R. H. THOMSON
hydroxyl. Shortly afterward Fieser showed that phthiocol could be obtained from vitamin K x by treatment with alcoholic alkali (179). This in
fact, occurs during the Dam-Karrer test (49) for vitamin K x , the
transient purple color changing to reddish brown as the anion of
phthiocol is formed.
Crystalline vitamin K 2 was first isolated in 1939 by Doisy and his
group from putrefied fishmeal (180). After extraction with light petroleum it was concentrated by chromatography and was finally crystallized
in light-yellow plates, m.p. 54°. A few years later Tishler and Sampson
(181) isolated the same vitamin from autolyzed cells of the soil bacterium Bacillus brevis. The structure was investigated by Doisy following the general procedure used in the study of vitamin K i? in particular,
ozonolysis of the leucodiacetate gave l,4-diacetoxy-2-methyl-3-naphthaldehyde, previously obtained from vitamin K 1? together with acetone
and levulinic aldehyde (nearly five moles). As these fragments accounted for forty-one carbon atoms, in agreement with the molecular
formula C 4 iH 5 60 2 , Doisy et al. proposed structure (CXXXII; n = 6) for
vitamin K 2 (182).
O
Me
Me
I
(CH 2 —CH==C—CH 2 )„H
O
Vitamin K 2
(CXXXII)
No further chemical work was done in the vitamin K field for about
ten years. In the meantime it had been observed that menadione
(2-methyl-l,4-naphthoquinone) derivatives lacking a side chain at position 3, could not, in all cases, replace vitamin K x in vitamin K therapy,
and this led to renewal of chemical and clinical investigation of the
natural vitamins, especially by Isler and his collaborators in Basel. Using
their immense experience in the synthesis of carotenoids they turned
their attention to the polyisoprenoid naphthoquinones and succeeded in
preparing a series of compounds with side chains containing two to
seven isoprene units (CXXXII; n = 2 to 7) (183). A remarkable outcome of this work was the finding that Doisy's quinone, m.p. 54°, was
not the difarnesyl derivative (CXXXII; n = 6) but 2-methyl-3-(alltrans) -farnesylgeranylgeranyl-l,4-naphthoquinone
(CXXXII; n = 7)
having a side chain of thirty-five carbon atoms. Furthermore, isolation
o5
R. H. THOMSON
hydroxyl. Shortly afterward Fieser showed that phthiocol could be obtained from vitamin K x by treatment with alcoholic alkali (179). This in
fact, occurs during the Dam-Karrer test (49) for vitamin K x , the
transient purple color changing to reddish brown as the anion of
phthiocol is formed.
Crystalline vitamin K 2 was first isolated in 1939 by Doisy and his
group from putrefied fishmeal (180). After extraction with light petroleum it was concentrated by chromatography and was finally crystallized
in light-yellow plates, m.p. 54°. A few years later Tishler and Sampson
(181) isolated the same vitamin from autolyzed cells of the soil bacterium Bacillus brevis. The structure was investigated by Doisy following the general procedure used in the study of vitamin K i? in particular,
ozonolysis of the leucodiacetate gave l,4-diacetoxy-2-methyl-3-naphthaldehyde, previously obtained from vitamin K 1? together with acetone
and levulinic aldehyde (nearly five moles). As these fragments accounted for forty-one carbon atoms, in agreement with the molecular
formula C 4 iH 5 60 2 , Doisy et al. proposed structure (CXXXII; n = 6) for
vitamin K 2 (182).
O
Me
Me
I
(CH 2 —CH==C—CH 2 )„H
O
Vitamin K 2
(CXXXII)
No further chemical work was done in the vitamin K field for about
ten years. In the meantime it had been observed that menadione
(2-methyl-l,4-naphthoquinone) derivatives lacking a side chain at position 3, could not, in all cases, replace vitamin K x in vitamin K therapy,
and this led to renewal of chemical and clinical investigation of the
natural vitamins, especially by Isler and his collaborators in Basel. Using
their immense experience in the synthesis of carotenoids they turned
their attention to the polyisoprenoid naphthoquinones and succeeded in
preparing a series of compounds with side chains containing two to
seven isoprene units (CXXXII; n = 2 to 7) (183). A remarkable outcome of this work was the finding that Doisy's quinone, m.p. 54°, was
not the difarnesyl derivative (CXXXII; n = 6) but 2-methyl-3-(alltrans) -farnesylgeranylgeranyl-l,4-naphthoquinone
(CXXXII; n = 7)
having a side chain of thirty-five carbon atoms. Furthermore, isolation
o5