2.6- dioxabicyclo- -octane

The squalestatins, e.g. 6.28, also known as the zaragozic adds, have attracted considerable interest as inhibitors of squalene synthase and hence of cholesterol biosynthesis and lipid deposition in the circulatory system. They are also inhibitors of farnesyl protein transferase and thus they may have other potentially useful biological applications. They are formed by Phoma spedes and also by Setosphaeria khartoumensis. The squalestatins are characterized by a dioxabicyclo-octane core bearing three carboxyl groups and two polyketide chains, one of which is attached as an ester. The biosynthetic incorporation of succinic acid into part of the bicyclo-octane, together with its oxygenation pattern, indicate that it may be derived via oxaloacetic acid. Both the polyketide chains have several pendant methyl groups attached to them, which arise from methionine, whilst benzoic add ads as a starter unit for one of the chains. These complex structures are thus the summation of several biosynthetic pathways. 

IS)-endo,endo-5-Ethyl-2,4-dimethyl-6,8-dioxabicyclo-[3.2.1]-octane [54832-20-1]... 

Contained within intermediate 25 is an acid-labile mixed acetal group and it was found that treatment of 25 with camphorsulfonic acid (CSA) results in the formation of dioxabicyclo[3.3.0]octane 26 in 77 % yield. Acid-induced cleavage of the mixed cyclic acetal function in 25, with loss of acetone, followed by intramolecular interception of the resultant oxonium ion by the secondary hydroxyl group appended to C leads to the observed product. Intermediate 26 clearly has much in common with the ultimate target molecule. Indeed, the constitution and relative stereochemistry of the dioxabicyclo[3.3.0]octane framework in 26 are identical to the corresponding portion of asteltoxin. 

Scheme 8.11 Regio- and stereocontrolled construction of the dioxabicyclo[3.2.1]octane skeleton of (+)-sorangicin A.

Polymerization of 6,8-dioxabicyclo[3.2.1]octane, 2, has been most extensively studied among bicyclic acetals. This monomer is readily prepared from 3,4-dihydro-2H-pyran-2-carbaldehyde 1 by reduction with sodium borohydride followed by add-... 

Methyl- and 5,7-dimethyl-6,8-dioxabicyclo[3.2.1]octanes were polymerized in bulk in the presence of a large amount of boron trifluoride24. The resulting polymers having molecular weights of 900—1130 melted at 95—97 and 102—105 °C, respectively. 

Polymerization of 4-bromo-6,8-dioxabicyclo[3.2.1 ]octane 2 7 in dichloromethane solution at —78 °C with phosphorus pentafluoride as initiator gave a 60% yield of polymer having an inherent viscosity of 0.10 dl/g1. Although it is not described explicitly, the monomer used seems to be a mixture of the stereoisomers, 7 7a and 17b, in which the bromine atom is oriented trans and cis, respectively, to the five-membered ring of the bicyclic structure. Recently, the present authors found that pure 17b was very reluctant to polymerize under similar conditions. This is understandable in terms of a smaller enthalpy change from 17b to its polymer compared with that for 17a. In the monomeric states, 17b is less strained than 17a on account of the equatorial orientation of the bromine atom in the former, whereas in the polymeric states, the polymer from 17b is energetically less stable than that from 17a, because the former takes a conformation in which the bromine atom occupies the axial positioa Its flipped conformation would be even more unstable, because the stabilization by the anomeric effect is lost, in addition to the axial orientation of the methylene group. 

Table 6.1H-NMR chemical shift changes of the cyclic hexamer of 6,8-dioxabicyclo[ 3.2.1 J-octan-7-one upon interaction with thiocyanate salts in deuterkjchloroforma...

As a first step in the prepartion of polymers patterned after the repeating unit of nonactin 56, Moore and Kelley53 synthesized 3,8-dioxabicyclo[3.2.1 ]octan-2-one 57 and its corresponding polyester 58. The monomer was prepared from 5-hydroxy-methylpyran-2-carboxylic acid in overall yield of 20%. It was heated with a catalytic amount of tert-butoxytitanate under nitrogen for 3 hr at 100 °C. The temperature... 

This prediction was borne out for reactions of 2,3-dioxabicyclo[2.2.2]octane 2 27) and the 7-substituted-[2.2.1]-peroxides 10201 and 1121) which afforded 62b-d respectively upon treatment with either methanolic KOH or triethylamine. The bismercurated-[3.3.2]-peroxide 47 reacted similarly with aqueous NaOH, but the resultant 5-hydroxycyclooctanone underwent further rearrangement to the internal hemi-ketal.49)... 

The mechanistic dichotomy (Eq. 50 and 52) that obtains in the thermolysis of 2,3-dioxabicyclo[2.2. l]heptane 9 has no equivalent with 2 and accordingly the abnormally large solvent effects found in the thermolysis of 9 were not observed for 2. In fact, the [2.2.2] system 2 is considerably more stable thermally than the [2.2.1] system 9. While 9 decomposes quite rapidly in cyclohexane at 60-80 °C, for 2 temperatures as high as 120-150 °C are needed to promote comparable rates the activation parameters are AH = 21kcalmor1and AS = — 19e.u.for2,3-dioxabieyclo[2.2.1]-heptane, and AH = 33 kcal mol-1 and AS = +3 e.u. for 2,3-dioxabicyclo[2.2.2]-octane 67). 

Dioxabicyclo[3.2.1]octan-4-one, enone 1,2-reduction with acetal, 129-130 Disubstituted alkenes, alkene to alkane reductions, 36-38... 

Reductive nucleophilic cleavage of the l-alkoxymethyl-6,8-dioxabicyclo[3.2.11-octanes 44 catalysed by TiCl4 leads to the formation of the oxepane derivatives 45 (eg. R = Me) in good yield <00T1065>. 

Fundamentally, D-glucofuranurono-6,3-lactone (4) contains the 2,6-dioxabicyclo[3.3.0]octane structure (5), just as do ido-, manno-, and... 

For the depiction of structural formulas of hexofuranoses, a combination of a three-dimensional, Haworth-perspective tetrahydrofuran ring with a Fischer projection of the C-5-C-6 side-chain is commonly used, as exemplified by formulas 3 and 6. With the formal closure of the second ring and formation of a 2,6-dioxabicyclo[3.3.0]octane system, however, the depiction of the C-6-C-3 ring, as in formula 7, also assumes three-dimensional geometry, and this does not correspond to the Fischer projection rule.11 Consequently, structural representations of such bicyclic molecules should be as close as possible to the actual steric situation, as shown by structures 4 and 8. 

---