Synthesis of Diacylated Trehalose Sulfates: Candidates for a Tuberculosis Vaccine

Abstract

Auf einer kurzen und generellen Route wurden Analoga des mycobakteriellen Sulfoglycolipid‐Antigens 1 aus Mycobacterium tuberculosis synthetisiert. Einige Derivate zeigten interessante immunogene Eigenschaften und aktivierten cytotoxische T‐Zellen. Sie enthielten eine chirale gesättigte oder α,β‐ungesättigte, mehrfach methylierte Fettsäure mit S‐konfigurierten Stereozentren an der 3‐Position des Trehalosekerns.

Copper‐Catalyzed Asymmetric Allylic Alkylation of Halocrotonates: Efficient Synthesis of Versatile Chiral Multifunctional Building Blocks

“…[29] These building blocks have been previously used for the synthesis of an alarm pheromone of Atta texana, [30] a high-potency sweetener NC-00637, [29a] and candidates for a tuberculosis vaccine. [31] We envisioned that these building blocks could be modularly constructed by a CM-olefin reduction sequence from 6a. With optimized conditions [21] for the non-transition metal-mediated reaction we were able to obtain (S)-15 in 89% conversion and 75% yield (Scheme 3) illustrating the possibility of assembling these highly warranted products using AAA.…”

Simplified Deoxypropionate Acyl Chains for Mycobacterium tuberculosis Sulfoglycolipid Analogues: Chain Length is Essential for High Antigenicity

“…[6][7][8] GM-CSF (granulocyte-macrophage colony-stimulating factor) released by the T-cells was quantified, and the results are summarized in Figure 1. [6][7][8] GM-CSF (granulocyte-macrophage colony-stimulating factor) released by the T-cells was quantified, and the results are summarized in Figure 1.…”

“…[7,8] In contrast, 21 d is highly antigenic, and it is as active as the natural product. We had shown earlier that 21 e was very weakly antigenic.…”

“…Removal of the silyl ether in 9 (90 %) followed by PCC oxidation gave aldehydes 10 a-d. Carboxylic acid 11 was obtained from 10 d by using a slight excess of Jones's reagent in acetone, whereas unsaturated acids 12 a-c were prepared by coupling of 10 ac with the Wittig reagent (carbethoxyethylidene)triphenylphosphorane, followed by saponification as previously described. [7,15] The other major challenge in the synthesis of the SGLs is the rapid construction of a trehalose-based core structure suitably protected to differentiate the 2-, 2'-, 3-, and 3'-positions. Solutions to the problem have usually resulted in a lengthy generation of the appropriately protected disaccharide building block.…”

“…The antigenicities of these new Acyl 2 SGLs were then assessed with the aid of the Acyl 2 SGL-specific T-cells. [6][7][8] GM-CSF (granulocyte-macrophage colony-stimulating factor) released by the T-cells was quantified, and the results are summarized in Figure 1. We had demonstrated earlier [7,8] that the number of methyl groups on the 1,3-methyl-branched fatty acyl chain of the SGL was an important structural element, with increasing antigenicity of the analogues as the number of methyl groups increased.…”