Lactone rule

The a-oriented lactone configuration (LXVIII) was originally favored by us (8) and by Stork and Newman (33). The latter authors arrived at this conclusion from their observed molecular rotation difference between the C-2-epi-tetrahydrogibberellic acid and the corresponding dibasic acid obtained by opening the lactone ring. They interpreted this value (+75°) in a rather doubtful manner in terms of Klyne s application (24) to polycyclic compounds of Hudson s lactone rule. 

The absolute chemistry of reserpine has been derived directly (135), by making use of Klyne s extension of the Hudson lactone rule (147) as applied to reserpic acid and its lactone, as well as by the application of Prelog s asymmetric synthesis (148) to methyl reserpate (149). These results are in agreement with the conclusions obtained by more indirect but no less accurate means (91). 

Fried, Walz and Wintersteiner isolated 4-desoxy-i/-glycero-tetrose phenylosazone (XLII) from the reaction of streptobiosamine hydrochloride with phenylhydrazine and thus demonstrated that streptose was configurationally an l sugar. The levorotation ([a] o —37°, water ) of streptosonic acid monolactone (XXIII) might also be adduced as contributory evidence for the l configuration of the penultimate carbon of streptose, should Hudson s lactone rule be applicable to this rather complex structure. 

In Figure 7 two views must be considered, one view along the OCO angle bisector and one from above. In Figure 7 the curved surface is a spherical distortion of the yz plane of the octant rule nodal plane (cf. also Subsection III.B.4). Other nodal surfaces remain planar. The signs refer to the back octants. Hence, the lactone rule is an octant rule with opposite signs. 

IX. Early Indications of Configurations by the Lactone Rule of Rotation. 18... 

The discovery of empirical rules of rotation of derivatives of the aldonic acids which indicated the configuration of the y-, and later the a-carbon atoms, made possible an advance in the solution of the problem of establishing the configurations of the synthetic higher-carbon sugars and the naturally-occurring rhamnose and fucose. The lactone rule was the earliest of these generalizations it was inferred from very extensive data. 

The first new result from the application of the lactone rule was the assignment of a complete configurational formula to natural rhamnose. The configuration of carbon atom 5 was indicated by the sign of rotation of the rhamnotetronic lactone, and therefore the Fischer formula could now be made complete it became... 

Digitoxose, therefore, represents a case wherein the Hudson lactone rule fails insofar as the lactones of digitoxonic and digitoxosecarboxylic acids are concerned, a behavior paralleled by D-allonic acid lactone of which digitoxose is a derivative. At the same time, the diamide of the glutaric acid obtained on oxidation of digitoxose now obeys Hudson s amide rule in the light of the above observations and also the lactone of this acid obeys the lactone rule. 

Although the adoption of Hudson s lactone rule allowed the tentative assignment of configuration, 3R,6R, to the (— )-tropan-3a,6)3-diol (37) (see Volume VI, pp. 161-162), corroboration by correlation seemed necessary. 6/3-Methoxytropinone 38) was resolved and correlated with natural valeroidine and with (S -methoxysuccinic acid 39a). The dextrorotatory ketone XXIX was converted into (— )-3 ,6 S-diacetoxytropane... 

Hudson lactone rule. The value of the rotation of aldonic acid lactones is decisively affected by the configuration of that carbon atom whose hydroxyl group is engaged in the cyclization. If, in the normal Fischer projection formula, the lactone ring is written on the right, the lactone is dextrorotatory if it is written on the left, the lactone is levorotatory. 

A comparison of the molecular rotations of lycorine and 2-epilycorine provided the first evidence for the absolute configuration of alkaloids of the lycorine type by the application of Mills rule. The development of suitable chemical methods of interconversion between the lycorine- and lycorenine-type alkaloids permitted an additional correlation between the two types by the Hudson-Klyne lactone rule. These assignments have recently been shown to be correct by X-ray crystallographic methods (65). With these findings the structure and absolute configuration of lycorine is described by I (R, Ri = H). The absolute configurations of many of the alkaloids discussed in Section III also are secure because these alkaloids have been interrelated and converted to known compounds of the lycorine series. 

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