Tandem synthesis of polypropionate chains–highly stereoselective synthesis of the ansa chain of streptovaricin U and protostreptovaricins based on stereospecific methylation of γ,δ-epoxy acrylates by trimethylaluminium

Abstract

The highly stereoselective synthesis of the ansa chain segment 23 of streptovaricin U and protostreptovaricins (I and 11) is achieved by stereospecific methylation of y,&epoxy acrylates with trimethylaluminium.

R3Al−R‘3SiOTf: Novel and Powerful Reagent System for Stereospecific Alkylation−Silylation Reactions of Epoxides

“…As shown, all the reactions proceeded stereospecifically giving rise to the corresponding silyl ethers of alkylation products as single products in excellent yields (entries 1−12). The configuration of the products was unambiguously confirmed by agreement with that of the products obtained by the reaction of 1 and 2 with the Gillman reagent (Me 2 CuLi),2a although the later reactions gave lesser yields (40 and 67%, respectively) of products. It is noteworthy that the reactions of trans- γ,δ-epoxy unsaturated ester ( 4 ) having no particular oxygen function on the side chain also occurred smoothly with complete regioselectivity at the γ-position to give single γ-substitution products (entries 9−12), which were in contrast with the very sluggish reaction of 4 with the Me 3 Al−H 2 O system resulting in the formation of an 80:20 mixture of γ- and δ-methylation products .…”

“…Stereoselective carbon−carbon bond-forming reactions of epoxides with carbon nucleophiles are one of the most important transformations in organic synthesis, particularly in natural product synthesis . Although various organoaluminum reagents have been used as carbon nucleophiles 3 for epoxide-opening reactions, this type of reaction is restricted to a structurally limited number of substrates such as 2,3-epoxy alcohols, γ,δ-epoxy unsaturated esters, epoxy sulfides, and so on and not applicable to simple epoxy alkanes themselves.…”

New Derivatives of Levoglucosan by Tandem Epoxide Allyl Alcohol Rearrangement‐Cuprate Cross‐Coupling

“…The yield was lower in the reaction of the ethyl Gilman cuprate because the commercial ethyllithium was very dilute and in this case 30 % of the tosylate 5 was also isolated. The branched (4R)-allyl alcohol fragment of the 1,6-anhydro sugar 6a is found in many macrolide fragments such as for example phorbazol, [34] streptovaricin, [35] or leinamycin. [36] The stereochemistry of the hydroxy group at C-4 of 6a is inverted with respect to the levoglucosan (1).…”

Highly Stereoselective Synthesis of anti,anti-Dipropionate Stereotriads: A Solution to the Long-Standing Problem of Challenging Mismatched Double Asymmetric Crotylboration Reactions

“…The examples shown in Table 1 and Scheme 1 provide a powerful demonstration of the high enantiofacial selectivity of reagents ( S )-( E )- 22 and its enantiomer ( R )-( E )- 22 . Notably, the all- anti -stereopentads embedded in 24d–g , which proved to be a significant challenge in syntheses of (+)-zincophorin 16 and (−)-streptovaricin U, 17 can be obtained in good yields and with excellent selectivities (>15:1 d.s. in the case of 24e ).…”