Reduced Pyrans

Alder reaction, catalysed by dimethylaluminium chloride, has been employed in a new total synthesis of pseudomonic acids A and C from hexa-1,5-diene. In a further study of the ionophore antibiotic lasalocid (3), it has been subjected to Mannich and Baeyer-Villiger reactions. The former took an unusual course in that the carboxyl was replaced by an aminomethyl group. The natural ionophore X-14547A (4) has been synthesized from two separately prepared segments (5) and (6) of the molecule.  

The conformation of 17-cp/-deoxysalinomycin (a close relative of the antibiotic) has a definite form in solution but it cannot exist as a head-to-tail hydrogen-bonded structure. The relevance of these deductions to its biological role has been discussed. One of the constituents of the secretion of the bee Andrena wilkella is the bis-spiropyran (7), and this has been synthesized from ethyl (+)-(5 )-3-hydroxybutenoate, obtained from the reduction of ethyl acetoacetate by yeast.  

The use of n.m.r. and chemical reactions in the determination of stereochemical assignments for reduced cyclopropapyrans (8) has been extended to the 7-phenyl derivative, which was synthesized from 5,6-dihydro-27/-pyran and a,o -dichlorotoluene. Reduction of the chloro-compound (8) with IiAlH4 gave the e c o-isomer (9), which was isomerized to the exo-form 

Tetrahydropyran-2-carboxylic acids are decarboxylated by concentrated sulphuric acid and the resulting carbonium ions, such as (14), are relatively stable this was demonstrated by n.m.r. spectroscopy. Qneolic acid (15), which was known to produce the lactone (17), also yielded the oxonium ion 

Wagner, Schriftenr. Bundesapothekerkammer Wiss., Fortbild., Gelde Reiche, 1978, 6, 81. 

Grisebach, Recent Adv. Phytochem., 1977,12 (Biochemistry of Plant Phenolics), p. 221. 

Masquelier, J. Michand, J. Laparra, and M. C. Damon, Int. J. Vitam. Nutr. Res., 1979, 49, 307. ACS Symposium Series, No. 98, Cannabinoid Analysis in Physiological Fluids , American Chemical Society, Washington, 1979. 

Sundholm, Acta Univ. Ups. Abstr. Uppsala Disc. Fac. Sci., 1979, 526. 

Saur and V. Ruzicka, Sb. Vys. Sk. Chem.-Technol. Praze, Org. Chem. Technol, 1978, C25, 77. 

---

The partially reduced pyrans (13) and (14) are named from 2/Z-pyran. The benzologue (15) is called chroman, whilst flavan is used for the 2-phenyl derivative (16). 

In contrast, a useful amount of information has accumulated on reduced pyrans, generally as a result of investigations into stereochemical features of these compounds. 

Interest in reduced pyrans centres around tetrahydropyrans and chromans. Many structural determinations have been reported for pyranoses and various derivatives (72PMH(5)l). 

REDUCED PYRANS AND PYRANONES AND THEIR BENZO DERIVATIVES ... 

Irradiation of reduced pyran-4-ones frequently gives dimeric products which sometimes revert to the monomer. 2,6-Dimethyl-2,3-dihydropyran-4-one (559) in water gives a 96% yield of a mixture of three dimers (560) in a reaction which is reversible (73CJC1267). 

Individual functional groups attached to a partially or fully reduced pyran ring behave much as expected of their aliphatic equivalents but there is often a quantitative difference in their reactivity which enables selective reactions to be carried out on polysubstituted compounds. Many examples of this are known in the tocopherol series which are the most important members of the chroman family. Since they are known by trivial names, these are shown with their structures (674). The most important tocopherol is natural vitamin E or a-tocopherol the four natural tocopherols have 7 -configuration at each of their asymmetric centres at C-2, C-4 and C-8. ... 

In this section, the three simple reduced pyrans (200), (201) and (202) are initially considered. Fused alicyclic analogues are included in this group. A discussion of the benzologues, chroman (203) and isochroman (204), and the reduced naphthopyrans follows. 

From a preformed heterocyclic ring (i) From reduced pyran-4-ones... 

The reaction of homophthalic acids or anhydrides with citral in the presence of pyridine yields reduced pyran-2-ones by means of an aldol condensation involving the activated methylene group of the acid. Dehydration is followed by an acid-catalyzed rearrangement to the pyran-2-one (Scheme 201) <79H(12)253). 

Interest has been expressed in the use of dihydropyranones as synthons for natural products and this has led to the development of a valuable route to 5,6-dihydropyranones. Electron-rich dienes bearing a trimethylsilyloxy substituent undergo cycloadditions with carbonyl compounds at room temperature in the presence of a Lewis acid (Scheme 210) (82JA358). The intermediacy of a reduced pyran has been postulated. 

Reduced Pyrans and Pyrones and Their Benzo Derivatives 399... 

Partially reduced pyrans are named as derivatives of 2//-pyran, for example, 3,4-di hydro-2//-pyran 13 and 3,6-dihydro-27/-pyran 14. The trivial name for the benzo analog 15 is chroman, and flavan is used for 2-phenyl... 

The synthesis of several natural reduced pyrans or fragments of these molecules has received much attention. The conversion of the protected monic acid A (9 R=0C02Bu) into the ketone (9 R=Bu) has been effected with butylmanganese chloride,27 and this is important in the study of pseudomonic acid A.28 The dihydropyran (10), a key intermediate in the synthesis of this natural acid, has been synthesized from the lactone (11) by reaction with dimethyl sodio-malonate and Pd( PPh3 ) , 29... 

---