Prelog-Djerassi lactone, preparation

Compound 17 is the so-called (+)-Prelog-Djerassi lactonic acid derived via the degradation of either methymycin or narbomycin. This compound embodies important architectural features common to a series of macrolide antibiotics and has served as a focal point for the development of a variety of new stereoselective syntheses. Another preparation of compound 17 is shown in Scheme 3-7.11 Starting from 8, by treating the boron enolate with an aldehyde, 20 can be synthesized via an asymmetric aldol reaction with the expected stereochemistry at C-2 and C-2. Treating the lithium enolate of 8 with an electrophile affords 19 with the expected stereochemistry at C-5. Note that the stereochemistries in the aldol reaction and in a-alkylation are opposite each other. The combination of 19 and 20 gives the final product 17. 

Acyl-l,3-oxazolidine-2-thiones, chiral (1). Nagao and co-workers1 have prepared the chiral 3-acetyl-l,3-oxazolidine-2-thiones (la and lb) and used them to effect diastereoselective aldol reactions. The two chiral auxiliaries show, as expected, opposite diastereoselectivities, but contrast with the diastereoselectivities observed with chiral 4-alkyl-2-oxazolidones (11, 379-381). This aldol reaction has been used to prepare the chiral azetidinone 4 (equation I) and (-I- )-Prelog-Djerassi lactone. 

The C—Si bond formed by the hydrosilation of alkene is a stable bond. Although it is difficult to convert the C—Si bond to other functional groups, it can be converted to alcohols by oxidation with MCPBA or H2O2. This reaction enhances the usefulness of hydrosilylation of alkenes [219], Combination of intramolecular hydrosilylation of allylic or homoallylic alcohols and the oxidation offers regio- and stereoselective preparation of diols [220], Internal alkenes are difficult to hydrosilylate without isomerization to terminal alkenes. However, intramolecular hydrosilation of internal alkenes can be carried out without isomerization. Intramolecular hydrosilylation of the silyl ether 572 of the homoallylic alcohol 571 afforded 573 regio- and stereoselectively, and the Prelog-Djerassi lactone 574 was prepared by applying this method. 

The cycloadduct (75d) has been utilized for the synthesis of nonactic acid (116) and lilac alcohol (119) via (118). The Prelog-Djerassi lactone (117), a pivotal intermediate in Masamune s methymycin synthesis, has been prepared tom the key compound (75e) (Scheme 21)J ... 

We will illustrate this strategy with an example found in the total synthesis of lysocellin by Yonemitsu [221,222]. As shown in Scheme 11.66, the Cl to C9 fragment was prepared by condensation of lactone 313 with the lithium salt of benzyl acetate. This part of the synthesis also serves as an illustration of sugar branching to reach a Prelog-Djerassi lactone type intermediate already mentioned in Section 11.3. A detailed discussion of this scheme follows. 

A related reagent (186) is prepared in three steps from (5)-atrolactic acid. The lithium enolate of (186) reacts with phenylacetaldehyde to give two aldols in a ratio of 94 6 (Scheme 12). [The full relative stereochemistry of aldols (187) and (188) was not rigorously determined, but may be deduced from the stereochemistry of (190). It is surprising that the lithium enolate of (186) has a diastereofacial preference that is opposite that of the related ketone (181).] Compound (186) has been used in a synthesis of the Prelog-Djerassi lactonic acid (191), as shown in Scheme 12. Reagents related to (181) and (186) have been used as their boron enolates for other synthetic purposes (see Chapter 1.7, this volume). 

The two other aldol products that can be derived via propionate addition to (24) are the Prelog-Djerassi lactonic acid diastereomers, both of which were prepared successfully with the internal chiral boron enolates discussed earlier in this section. Thus this work completes a set of chiral reagents that can control the relative stereochemistry at the 2,3 and 4 positions of aldol products. 

Rodriguez and co-workers envisioned the Carroll rearrangement as the key step in the preparation of the Prelog-Djerassi lactone 204. The dienolate of 200 conveniently rearranged via a chair-like transition state 201 to the y0-keto acid which underwent decarboxylation to give a 4 1 mixture of cyclopentanone epimers. Epimerization under thermodynamic conditions... 

Several synthesis of the Prelog-Djerassi lactone elevate the compound almost to the position of cis-jasmone in terms of its popularity as a synthetic target. Full details of the Danishefsky route to ( )-quadrone have appeared as well as a report of a concurrent synthesis. A new method for the preparation of 5-lactones involving the reaction of a y,5-unsaturated aldehyde with NaOH followed by oxidation has been applied to the synthesis of ( )-pentaleno-lactone. The first total synthesis of (+)-compactin has been reported. ... 

Methods for the preparation of optically active compounds have been reviewed. Still and his co-workers recently developed the hydroboration of acyclic 1,4-dienes as a method for the controlled creation of stereocentres. Two groups have now exploited this method in a short synthesis of the Prelog-Djerassi lactone (111). The key step in both routes is the hydroboration-oxidation of (109) to (110) that is highly stereoselective with respect to three of the four stereocentres of (110). 

Another of the earhest uses of an intermolecular [4+3] cycloaddition reaction was the stereoselective preparation of the synthetic intermediate, the Prelog-Djerassi lactone 29 [17]. This lactone is an important intermediate for the preparation of macrolide antibiotics [18]. The authors were also one of the first to use the [4+3] cycloaddition to stereoselectively install multiple stereocenters simultaneously and to transform the core cycloadduct into another molecular entity. 

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