Five-membered lactone ring

FIGURE 11.7 Cardiac glycosides consist of a sugar, a steroid skeleton, and a lactone ring. A five-membered lactone ring as here occurs in the cardenolide type. 

Usually y.B-unsaturated acids (260) are employed in these lactonizations. The initial step involves an electrophilic attack at the double bond, either by a proton or a reagent X—Y (264). An activated species (261) is thus generated, suitable for the nucleophilic addition of the carboxy group, which in principle may close to a six- or five-membered lactone ring (263 or 262 equation 92). Normally, (262) is preferred on the basis of vector approach analysis. 

Another alkaloid with the oxazolidine system is samandaridine (XVII), C21H31NO3, also a secondary amine. Chemical reactions (9) and IR-spectra indicate that it possesses a five-membered lactone ring. Its structure was also elucidated by X-ray analysis. Samandaridine hydrobromide crystallizes from methanol in monoclinic prisms its space group is C2 with four molecules in the unit cell. The cell constants are a = 14.50 A, b = 6.15 A, c = 22.52 A, = 94° (10). 

A second alkaloid without the oxazolidine ring, but with the carbino-lamine system is cycloneosamandaridine (XXVII). The IR-spectrum evidences a five-membered lactone ring (band at 1780 cm i) as well as the carbinolamine group (bands at 1050/1180 cm i). The IR-spectrum of the X-acetyl compound no longer shows these hands at 1050-1180 cm i, hut an additional carbonyl frequency at 1735 cm i for an aldehyde group. The mass spectrum confirms the molecular formula as well as structure XXVII(id). 

In the laboratory of J.L. Wood, an expeditious approach to the densely functionalized isotwistane core of CP-263,114 was developed. For the proposed radical cyclization, an exo-methylene group was installed on a five-membered lactone ring. It was discovered that both the formation of the lactone ring and the Eschenmoser methenylation could be conducted in a one-pot operation by simply treating the a-acetoxy ketone with excess amounts of LiTMP and then with Eschenmoser s salt. 

Laevifonol (761) is an e-viniferin-ascorbic acid hybrid compound, possessing a five-membered lactone ring, isolated from the heartwood of Shorea laeviforia [265]. The stem bark of Shorea hemsleyana yielded shorealactone (762), the structure and absolute configuration of which was determined by means of 2D NMR techniques and X-ray analysis of its 4-bromobenzoyl derivative [340]. H-7a and H-8a in laevifonol (761) were presented as cis. However, the authors did not provide evidence to support this. So, considering their similar NMR data and [a]o values [-200° (c 0.1, MeOH) for 762 and -124° (c 0.496, MeOH) for 761], we suggest that compounds 761 and 762 are the same compound. 

The lactones, the cyclic esters of hydroxy acids have been polymerised with various catalysts anionic catalysts, cationic catalysts and organometallic catalysts [28, 29, 39, 45, 54]. Five member lactone rings are unpolymerisable. Four, seven or eight member lactones are polymerisable [28, 29, 39, 45, 54]. 

Hydroxyphthalide derivatives have been formed from open-chain precursors via an enaminoketone derived with ammonia in which process either terminal keto system appears open to reaction. Prior formation of the five-membered lactone ring apparently occurs (ref.59). 

This type of comparatively simpler Cao-diterpenoid alkaloids bears a pentacyclic core in the structure. Only two new compounds named delphatisine C (44) from D. chrysotrichum [42] and honatisine (45) from D. honanense [43] have been isolated between the periods of 2009 and Feb. 2012. Compound 44 contains a five-membered lactone ring connecting to the oxazolidine ring. Extensive NOESY experiments were required to elucidate the relative configuration. Compound 45 is a novel C2o-diterpenoid alkaloid containing an unique l, 3, 5 -trimethyl-4 -oxocyclohexyloxy unit attached to C-24. 

Almost all types of oxygen functionalities are present in this class of steroidal lactones, and the characteristic IR spectral bands for various functionalities appear in the spectra. The characteristic enone and a,) -unsaturated Mactone moieties of withanohdes show absorptions at or near the 1,660 and 1,710 cm, respectively. An IR absorption at 1,778 cm is due to carbonyl stretching vibrations in five-membered lactone ring, found in all physalins and other classes of withanolides with modified skeleton [34-36]. 

The chiroptical properties of aldohexono- and aldopentono-1,4-lactones and some of their 2- and 3-deoxy derivatives have been discussed in terms of the conformation of the five-membered lactone ring, It is possible to decide whether these y-Iactones exist in solution in an or Ez conformation from c.d. measurements - for example, o-ribono- and D-allono-1,4-lactones prefer an E conformation (517), while D-talono-l,4-Iactone prefers an conformation (518). 

Interestingly enough, introduction of the double bond into the five-membered lactone ring introduces some extent of strain and makes its polymerization feasible as it was observed for a-angelicalactone (Structure 1). ... 

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