Lactone rule of rotation

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 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 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... 

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. 

Absolute configurations were first assigned to alkaloids of this section both by chemical transformations to compounds in the lycorine series where Mills rule had been applied and by Klyne s modification of the Hudson lactone rule. This extension states that lactones possessing the absolute configuration of XLVII are more positive in molecular rotation than derivatives in which the lactone ring is opened. If this rule is applicable to the alkaloids of this section, the conversion of homolycorine (XLVIII [M]d -f-268°) to tetrahydrohomolycorine (XLIX [M]d —322°) requires that homolycorine and tetrahydrohomolycorine have the absolute configurations shown in XLVIII and XLIX. These assign-... 

The configurations of the hydroxyl groups on carbons 4 and 5 have a major influence on the rotations of lactones. The lactone rule in its qualitative form (18) stipulates that a lactone is more dextrorotatory than the free... 

The absolute configuration of annotinine shown in I was resolved by Wiesner et al. (76). Three independent methods were used, all of which led to the same conclusion. The ORD-curve of XXVI, the relative stereochemistry of which has been demonstrated, showed a negative rotation maximum at 322 mp, [a] — 3450°. Application of the octant rule led to the absolute configuration shown in structure XXVI. Application of Hudson s lactone rule on annotinine hydrate led to the same conclusion. The Prelog method, when applied to compound VII, which must have the C-11 hydroxyl group cis to the bridge, was in agreement with the other methods. 

The directions of the optical rotations of the lactones (presumably gamma lactones) and phenylhydrazides of the four 3-deoxypentonic acids are in agreement with those predicted, on the basis of the assigned configurations, by the lactone and phenylhydrazide rules. 

---