Ortholactones

Thermolysis of 2,5-dihydro-l,3,4-thiadiazole 30 in CgDsCl solution at 20-35 °C gave spirothiiranes 43 and 44, O-hydrogen 0,0,A-ortholactone 45, the thio-A-ester 46, and 0,A,A-ortholactone 47 (Scheme 4) <1997HCA1260>. The ratio of these thermolysis products did not significantly vary between 23 and 35 °G. 

Spiroethers 241 and spiroketals 242 can be easily prepared by condensation of readily available annelating agents such as 106a with cyclic ketones, for example 243 and ortholactones 244, respectively. Both spiro-derivatives 241 and 242 are obtained in excellent yields (Scheme 13.88). 

The stereoselective formation of spiroketals 242 can be explained in terms of the thermodynamic stability of the three possible products. Oxonium cation 245, formed by the condensation of ortholactone 244b and allylsilyl ether 106a, is in equilibrium with the starting materials. Spiroketal 242 also equilibrates under the reaction conditions with the other anomers. The thermodynamically more stable product 242b, stabilized by a double anomeric effect, is obtained as the only product of the reaction (Scheme 13.89) as the substituents attempt to occupy equatorial positions in the newly generated tetrahydropyran ring. 

The orthosomycin antibiotics [46] are stmcturally characterized by one or more interglycosidic spiro-ortholactone linkages, replacing the traditional acetal junctions [47]. The natural occurrence of orthoesters is rare, but within recent years several examples of antibiotics possessing this common stmctural feature have been described. The orthosomycins include flambamycin, the eveminomicins-B, -C, -D and -2, hygromycin, the destomycins-A, -B and -C and the antibiotics SS-56-C and A-396-I (O Fig. 7). The orthosomycins have been divided into two... 

In 1999, new cycloparvifloralone-type sesquiterpenes were reported to consist of a unique acetal-hemiacetal and/or ortholactone structure as shown in Fig. (11). Cycloparvifloralone (65) occurred in the leaves oil. parviflorum, and (ll)7,14-ortholactone-14-hydroxy-3-... 

Fig. (12). Acetal and aldehyde, and ortholactone and lactone equilibrium of cycloparvifloralone-type sesquiterpenes 68, 73 and 74...

An intramolecular Lewis-acid catalyzed addition of an enol silyl ether to the spiro-ortholactonic center of 8 took full advantage of the stereoelectronic... 

Scheme 13.12 Johnson-Claisen rearrangement of an ortholactone-derived substrate.

Kocienski and his co-workers have described the novel intramolecular Lewis acid catalysed directed aldol reaction of the spiro-cyclic ortholactone (18 ) prepared from the fragments (185) and (186), to set up the spiro-acetal portion (I88). Milbemycin (189) was then secured from (I88) by sequential sulphone-based (Julia) olefination reactions to produce the double bonds at C10-... 

To improve the yield [211], treatment of the crude product of the Claisen rearrangement with thionylchloride is recommended, in order to bring the incidentally formed ortholactone 125 back to the main reaction pathway (Reaction scheme 79). 

Ortholactones such as 10 can be prepared from the corresponding 1-bromo-glycosyl cyanide by treatment with the alcohol in the presence of silver triflate and 2,6-lutidine, 8 and bromoimino-lactones such as 11 are the products formed by treatment of 0-protected glycosyl azides with NBS under photolytic or free-radical initiation.l O... 

Tetramers containing deoxy-sugars to have been synthesised are O-a-D-Galp-(l->3)-0-a-D-Glg7-(l- 3)-0-a-L-Rh -(l- 4)-D-ribitol, an 5. Pneumoniae polysaccharide unit, and a tetrasaccharide component of the orthosomycins (Chapter 19) containing a spiro-ortholactone feature. 

A full account has been given of the preparation of anomeric ortholactones from 1,1-dihalogeno-l-deoxypyranoses (see Vol. 22, p.160).23 Nojirimycin 5-lactam (23) has been prepared from 1.2 5,6-di-0-isopropylidene glucose by a sequence involving two inversions at C-5.24 Structures of type (24), in which an oligopeptide is attached to a carbohydrate at one end and to a 9-anthracenecarbonyl group at the other, have been synthesized to study their interaction with lipid bilayers.25... 

A stereoselective Claisen rearrangement occurs when butyro-ortholactones are heated with allylic alcohols the products are substituted butyrolactones. In contrast to the low dienophilicity that is usually observed for a -unsaturated lactones, the ester lactone (159) readily undergoes stannic-chloride-catalysed Diels-Alder reaction at room temperature. 3-Thiolen-2-one (160) is a useful... 

Synthesis of two isomers of the apiro-ortholactone part of the C-D fragment of orthosomycins has been described (Scheme 3) ... 

The ortholactone 14 could be prepared from the 0-benzylated 2-deoxylacmne by sequential treatment with triethyloxonium tetrafluoroborate and sodium ethoxide. Subsequent orthoester exchange could be effected with 1,2-diols to give spiroortholactones such as 15. When the glucosyl thiohydroximate 16, or its a-aiKHno, was photolysed in the presence of NBS, the spiro-oxathiazole 17 was obtained in 50% yield. 

The intramolecular cyclization strategy is applied to efficient synthesis of oxa-cycles starting with trimethylsiloxy-containing allylic silanes (Scheme 5.8). Treatment of 30 with benzaldehyde in the presence of a catalytic amount of McjSiOTf and PrOSiMej gives tetrahydropyran 32. An oxonium ion intermediate (31) is considered to be generated first and then undergo intramolecular nucleophilic attack by an allylsilane part [15]. When ortholactones are employed in lieu of aldehydes, spiroketals are readily prepared. 

---