Prelog-Djerassi lactonic acid, synthesis

As a model study for this methodology, Evans and Bartroli carried out the synthesis of (+)-Prelog-Djerassi Lactonic acid 47 [14b] [27], which is a degradation product of either methymycin or narbomycin [28] and has some of the important structural features present in macrolide antibiotics. 

Note that aldol condensations I, II and III concern the creation of a relative configuration 2,3-syn, which can be easily achieved starting from the (Z)-enolates 74a-74c. Scheme 9.27 summarises the synthesis of 93 and 95, which are equivalent to fragments B and A, respectively. Compound 88 is the abovementioned Prelog-Djerassi lactonic acid 42 which is obtained in optically pure from (>98% ee). On the other hand, for the stereochemical control of the aldol condensation IV a different methodology is necessary whih involves the coupling of two structurally predefined reactants and which will not be discussed here (Scheme 9.28). An important feature of this reaction is that the coordination of Li" " with the oxygen atom at the P-position of the aldehyde 95 is mainly responsible for the observed stereoselection [22e]. 

Like enamines, dihalocarbenes add smoothly to enol ethers and in many cases it is possible to isolate the dihalocyclopropyl intermediates which are valuable synthons for chloroenones (cf. Section 4.7.3.7.1). The earliest example of the addition of a dihalocarbene to an enol ether was provided by Parham,6,79 who studied the addition of dichlorocaibene to dihydropyran (equation 22). An example which illustrates the synthetic potential of the process is the conversion of the cyclohexanone enol ether (6) to the dichlorocy-clopropane (7 equation 23).80 The latter served as a useful intermediate in a stereospecific synthesis of Prelog-Djerassi lactonic acid. 

The BF,-etherate-catalyzed reaction of 1 with the aldehyde 2 provides a short stereoselective synthesis of the Prelog-Djerassi lactonic acid 3. 

A new approach to the synthesis of Prelog-Djerassi Lactonic acid (1) is reported. A key step in this synthesis involves an Ireland-Claisen rearrangement/silicon-mediated fragmentation sequence to provide the carbon framework in (1). 

With the full complement of stereogenic centres required, the 1,3-diol (11) was then taken through a protection/ deproteclion sequence to afford the corresponding diacetoxy alcohol (13), thereby completing the formal synthesis of (+)-PDLA. The remaining steps in the total synthesis followed the route employed by Yamaguchi and co-workers/ Diacetoxy alcohol (13) was oxidised with RuClj/NalO to provide acid (14), which underwent concomitant lactonisation to (15) under saponification conditions. The primary alcohol (15) was then oxidised to afford (+)-Prelog-Djerassi lactonic acid in an overall 9 % yield, with all spectroscopic data in accord with the literature values. 

For a review concerning the synthesis of Prelog-Djerassi lactonic acid, see S. F. Martin and D. E. Guinn, Synthesis, 1991,245 and references cited therein. 

Isobe, M, Ichikawa, Y, Goto, T, Total synthesis of (+)-Prelog-Djerassi lactonic acid. Tetrahedron Lett., 22, 4287-4290, 1981. 

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 facial selectivity of (43) was found to be 1.75 1 from the ratio of aldol products (48) and (49) obtained by the reaction with the achiral boron enolate (50). The latter is structurally similar to reagents (37) and (38). These experiments confirm again the validity of the rule of double asymmetric synthesis. The product (44) can be further converted through a sequence of reactions to provide (+)-Prelog-Djerassi lactonic acid (51 Scheme 27) (i) trimethylsilylation (ii) hydroboration with thexylborane (single asym-... 

Laevoglucosenone provides short, stereoselective routes to chiral synthons leading to (-)-S-multistriatin and (+)-Prelog-Djerassi lactonic acid (84)(see also Vol.16, p.265). The allo-oxiran (85) (obtained from D-glucose) has been used as the chiral control in a synthesis of chrysanthemic acids (86)(Scheme 17), the cyclopropane ring being formed by Wadsworth-Emmons reaction. ... 

Scheme 3. While asymmetric induction using chiral aldehydes to achieve selectivity usually provides modest results (a), incorporation of an auxiliary provides excellent induction (b) as demonstrated in Evans total synthesis of the (+)-Prelog-Djerassi lactonic acid (34). (1982) ...

Some interesting examples of levoglucosenone s application in the synthesis of natural products and rare carbohydrates have been reported (58-81). Indeed, levoglucosenone has been used in the synthesis of (+)-multistriatin (58,72-73), Prelog-Djerassi lactonic acid (58,59) md (-)-a//o-yohimbane (61) The synthesis of indole alkaloid reserpine (61), and serricomin (58), as well as tetrodotoxin (53,62) were also reported from levoglucosenone or its functionalized derivatives and was reviewed earlier by us (1). 

Chiral boron enolates are effective in enantioselective aldol condensations, a transition-state model being proposed for the moderate chirality transfer exhibited (Scheme 57). ° Diastereoselection with chiral lithium enolates has also been demonstrated by a highly stereoselective synthesis of the Prelog-Djerassi lactonic acid. ... 

A review of syntheses of the Prelog-Djerassi lactonic acid includes carbohydrate-based routes,27 and there have been two further reports of syntheses of the P-hydroxy-5-lactone unit (38) of mevinic acid and its congeners.28, 29 jn a synthesis of the mosquito oviposition pheromone (39), the chiral centres were derived from those of 2,3-0-ethylidene-D-erythrose, with this chiron being extended by Wittig reactions, in a similar manner to the use of 2-deoxy-D-ribose in an earlier approach to the same target (S.-K. Kang and I.-H. Cho, Tetrahedron Lett., 1989, 30, 743). 

Y. Yamamoto and K. Maruyama, Organometallic Compounds for Stereo-regulated Synthesis of Acyclic Systems. Their Application to the Synthesis of the Prelog-Djerassi Lactonic Acid , Heterocycles, 1982, 18, 357. 

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