Spirolactones synthesis

In 1994, Quayle et al. reported the application of this cyclic Fischer-carbene synthesis from 3-butynols to spirolactone synthesis, although the process was stepwise and a stoichiometric amount of the complex was employed [17]. The key transformation was the chromium or tungsten carbene complex formation followed by the CAN oxidation of the complex to give y-lactone. The reaction was further applied to the synthesis of andirolactone and muricatacin, the former being shown in Scheme 5.14. 

Spirofuran-2(5H),2 (3 H)furo[2,3-6]furan synthesis, 4, 659 Spirofuranones synthesis, 3, 734 Spiro[3.3]heptane physical properties, 1, 590 Spiroindazoles irradiation, 5, 252 Spiroisoarsindolinium salts, 1, 544 Spiroisoxazolines synthesis, 6, 108 Spirolactones synthesis, 3, 846-847 Spiro-/3-lactones synthesis, 7, 395 Spiro nomenclature, 1, 26 Spirooxadiazoles synthesis, 4, 822 Spirooxaziridines photorearrangement, 7, 541 (8-scission, 7, 211 Spirooxetanes synthesis, 7, 393 Spirooxiranes cleavage... 

SCHEME 16.24. Enantioselective spirolactone synthesis through Michael/nucleophilic substitution organocascade. 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

Total synthesis of a novel antibiotic, aranorosin (23), which was isolated from the fermentation broth of Pseudoarachniotus roseus, was accomplished by Rama Rao et al. [98], Wipf et al. [99], and McKillop et al. [100] via the construction of spirolactone (141) using PIFA or PIDA (Scheme 14). 

An interesting approach toward the total synthesis of the Stemona alkaloid, (-)-stenine (25), which have been used in Chinese and Japanese folk medicine as insecticides, as drugs for the treatment of respiratory diseases, via spirolactone... 

In the case of steroidal propargylic alcohols the first rearrangement produced a mixture of allenyl sulfoxides, epimeric at the sulfur atom, which reacted with an added nucleophile to produce substituted allylic sulfoxides. Rearrangement of the sulfoxide resulted in the exclusive formation of a-hydroxy derivatives. This reaction sequence has been applied in a synthesis of hydrocortisone acetate74 (Nu = OCH3) from androstene-3,17-dione and in a transformation of mesantrol75 (Nu = malonate) to a spirolactone. 

Similar condensations can be accomplished with other types of stabilized carbanions, e.g. sulfonyl anions, as illustrated by equation (81). The resulting sulfonyl lactone (228) eliminates sulfinic acid on treatment with p-TsOH to furnish the a,3-unsaturated system (229).Spirolactonization is the result of the Reformatsky reaction of ester (231) with cyclic ketones. In equation (82), this reaction is applied to the synthesis of the lysergic acid precursor (232), which is formed stereoselectively from (230). ... 

Tyrosine spirolactones are not only promising synthetic intermediates for bioactive natural products such as alkaloids and antibiotics but also synthons useful in peptide chemistry. For example, N-protected tyrosine derivatives 104 and 105, prepared from 2,6-di(ferf-butyl)-4-chloromethylphenol, were electrolyzed at a controlled potential (+1.3-1.4 V Vi. Ag/Ag+) in MeCN to give spirolactones 106 and 107 (64 and 85%, respectively). These spirolactones are used for peptide synthesis, as shown in Scheme 19. 

Other Reactions.—Addition of lithium /3-lithiopropionate to androstenolone leads to the synthesis of the spirolactone (101). Reaction of the lactone (102)... 

The /9-fragmentation of alkoxyl radicals generated from oxabicyclic hemiacetals of the [w.m.O] type is an attractive method for the synthesis of medium-sized and macrolactones by ring expansion reactions (Eq. 7 [36] and Eq. 8 [37], Scheme 3). Moreover, spirolactones can be prepared by fragmentation of other types of oxabicyclic hemiacetals such as 2-oxabicyclo[2.2.2]octan-l-ol and 6-oxabicyclo[3.2.1j-octan-5-ol (Eqs. 9, 10) [36b]. 

The first total synthesis of tryptoquivaline G (FTG) was achieved by Biichi et al. (158) (Scheme 15), which confirmed the proposed structure and established the relative and absolute configurations. Subsequently, Ban s group (159) effectively prepared Biichi s intermediate (90) through thallium(III) trinitrate (TTN) oxidation at a crucial step of spirolactonization. More recently, Hino s group achieved a short-step total synthesis of tryptoquivaline (160,161) and tryptoquivaline G (162) through oxidative double cyclization of the N-acyltryptophan precursor with A-iodosuccinimide (NIS) in CF3COOH (Scheme 16). 

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