Spiro compounds natural

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

Diarylamides with arenes activated by electron-donating substituents can be converted to azacycles by anodic oxidation through phenolic oxidative coupling reactions that can be a key step in the synthesis of alkaloids (Schemes 16 and 17). According to the nature of substituents and the experimental conditions, either spiro compounds [22] or non-spiro compounds [23, 24] were obtained. 

In principle, the approach outlined above for the a-oxoamides can be applied to any reaction, ground or excited state, which converts an achiral reactant into a chiral product, and Toda, Tanaka, and coworkers have investigated a wide variety of such processes [ 15,16]. A complete discussion of their work is beyond the scope of this review, and we illustrate the general approach taken with one final example. As shown in Scheme 4, irradiation of crystalline complexes of ene-diones 20a-f with chiral host (R,R)-(-)-9b led to cyclized products 21a-f in the variable yields and ee values indicated in Table 1 [22]. Remarkably, for reasons that were not clear (there was no accompanying X-ray crystallography), the R=n-propyl derivative 20g was found to give a completely different photoproduct, spiro compound 22 (69% yield, 97% ee, stereochemistry unknown), a result that once again illustrates the rather capricious nature of the use of chiral hosts for asymmetric induction. 

We have met diosgenin as an example of a natural spiro compound (see Box 3.17), and further examination of the structure shows the double bond as in cholesterol, a second five-membered ring c/s-fused onto the five-membered ring D, as well as the spiro fusion of a six-membered ring. Before this structure dismays you, take it slowly and logically. It should not be too difficult to end up with the stereodrawing shown here. 

Excellent yields are also obtained in spiro-adducts formed by the condensation of azomethine ylid thus generated, with 3-arylidene-flavanone derivatives at room temperature in the presence of trifluomethylacetic acid in toluene. These molecules are both flavonoids and spiro compounds, two classes of naturally occurring substances which exhibit biological activities 419... 

Griseofulvin is an example of a rare structure in nature, a spiro compound. The structure of griseofulvin was determined by Grove et al. " to be 7-chloro-2, 4,6-trimeth-oxy-6 3methylspiro benzofuian-2(3//)-r- 2jcyclohexenel-3,4 -dione. The compound is a white, bitter. heat-.stable pow-... 

Identification of some unstable natural products has been based on the identification of their adducts with PTAD (82P739 83JA4829 91HCA-2035). The same method has also been used for the identification of some unstable intermediates. For example, unstable 1,3,6,6-heptatetraene (divi-nylallene), which is formed by treatment of 172 with potassium hydroxide, can be trapped by excess PTAD to give spiro compound 173 (75AG492). 

These two examples rely on the rigidity of n systems but this simple saturated system is also chiral. These two rings have to be orthogonal because of the tetrahedral nature of the central carbon atom. There is no chiral centre, but there is no plane of symmetry. Cyclic compounds like this with rings joined at a single C atom are called spiro compounds. Spiro compounds are often chiral even when at a first glance they look quite symmetrical, and you should look particularly carefully for planes of symmetry when you think about their stereochemistry. 

The combination of the three-component domino Knoevenagel/Diels-Alder/epimerization allowed the construction of structures that with suitable modification gave the natural product-like cores as reported in a work of 2007 [87]. Hence, 1,3-dicarbonyl compounds 182 with benzaldehydes 4 and ( )-4-phenyl-3-buten-2-one 183 in the presence of a catalytic amount of (5)-5,5-dimethyl thiazoli-dinium-4-carboxylate 184 produced corresponding spiro compounds 185 in good yields (50-80%) and high diastere-oselectivity [dr (cis/trans) >99 1] (Scheme 2.61). 

Figure 5.49 shows some natural (the first two compounds) and unnatural (the second two compounds) spiro compounds. Of course, the distinction is purely formal—the chemical laboratory is part of Nature. 

In this chapter, the stereoselective synthesis of spiro compounds will be highlighted, with emphasis on the nature of the substituents on the spirocenter. In the first part of this review, we will give an overview of the recent methods leading to the formation of a quaternary spirocenter. This section will be structured around the nature of the metal catalyst. Next, the synthesis of spiro compounds having one or two heteroatom substituents will be disclosed in two distinct paragraphs (Figure 9.1). 

---