948859-72-1Relevant academic research and scientific papers
Total synthesis, stereochemical elucidation and biological evaluation of Ac2SGL; A 1,3-methyl branched sulfoglycolipid from Mycobacterium tuberculosis
Geerdink, Danny,Horst, Bjorn Ter,Lepore, Marco,Mori, Lucia,Puzo, Germain,Hirsch, Anna K. H.,Gilleron, Martine,De Libero, Gennaro,Minnaard, Adriaan J.
, p. 709 - 716 (2013)
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), continues to represent a challenging pathogen causing many deaths. A reason for the persistence of this pathogen is the cell-envelope composition, which consists of long-tailed (glyco)lipids, involved in the modulation of the host immune response. Diacylated sulfoglycolipid Ac2SGL (1), found in the cell envelope, is a potent antigen that stimulates the immune response towards TB. This observation suggests the application of 1 as part of a vaccine. Here, we report the first asymmetric total synthesis of 1. Two approaches were developed for the synthesis of hydroxyphthioceranic acid (4), its polypropionate part, thereby establishing the absolute stereochemistry of the C17 hydroxyl function to be of (R)-configuration. Subsequently, 4 was regioselectively connected to the trehalose core and after selective sulfation and a final fourfold deprotection step, pure 1 was obtained. The identity of synthetic and natural 1 was confirmed by NMR and mass analysis, Furthermore, synthetic 1 shows identical biological function to 1 and activates CD1b-restricted and Ac 2SGL-specific T cells that are highly sensitive to minimal structural modifications of 1 with the same potency. A modeling study is presented to point out the structural features of 1 that are important for binding to the antigen-presenting molecule CD1b and to the T-cell receptor. The Royal Society of Chemistry 2013.
Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision**
Cunha, Ana V.,Havenith, Remco W. A.,Holzheimer, Mira,Minnaard, Adriaan J.,Schouten, Stefan,Sinninghe Damsté, Jaap S.
supporting information, p. 17504 - 17513 (2021/07/06)
Crenarchaeol is a glycerol dialkyl glycerol tetraether lipid produced exclusively in Archaea of the phylum Thaumarchaeota. This membrane-spanning lipid is undoubtedly the structurally most sophisticated of all known archaeal lipids and an iconic molecule in organic geochemistry. The 66-membered macrocycle possesses a unique chemical structure featuring 22 mostly remote stereocenters, and a cyclohexane ring connected by a single bond to a cyclopentane ring. Herein we report the first total synthesis of the proposed structure of crenarchaeol. Comparison with natural crenarchaeol allowed us to propose a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted.
Asymmetric Total Synthesis of Mycobacterial Diacyl Trehaloses Demonstrates a Role for Lipid Structure in Immunogenicity
Holzheimer, Mira,Reijneveld, Josephine F.,Ramnarine, Alexandrea K.,Misiakos, Georgios,Young, David C.,Ishikawa, Eri,Cheng, Tan-Yun,Yamasaki, Sho,Moody, D. Branch,Van Rhijn, Ildiko,Minnaard, Adriaan J.
, p. 1835 - 1841 (2020/08/26)
The first asymmetric total synthesis of three structures proposed for mycobacterial diacyl trehaloses, DAT1, DAT2, and DAT3 is reported. The presence of two of these glycolipids, DAT1 and DAT3, within different strains of pathogenic M. tuberculosis was co
Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica
Geerdink, Danny,Buter, Jeffrey,Van Beek, Teris A.,Minnaard, Adriaan J.
, p. 761 - 766 (2014/05/06)
Virgin females of the parasitoid wasp Trichogramma turkestanica produce minute amounts of a sex pheromone, the identity of which has not been fully established. The enantioselective synthesis of a putative component of this pheromone, (6S,8S,10S)- 4,6,8,10-tetramethyltrideca-2E,4E-dien-1-ol (2), is reported as a contribution to this identification. Catalytic asymmetric conjugate addition of methylmagnesium bromide and stereoselective Horner-Wadsworth-Emmons olefinations are used as the key steps, and 2 was obtained in 16 steps with an overall yield of 4.4%.
A concise asymmetric synthesis of (-)-rasfonin
Huang, Yange,Minnaard, Adriaan J.,Feringa, Ben L.
supporting information; scheme or table, p. 29 - 31 (2012/01/19)
A very efficient total synthesis of the apoptosis inducer (-)-rasfonin has been developed using CuBr/JosiPhos catalyzed iterative asymmetric conjugate addition of MeMgBr and Feringa's butenolide.
Formal synthesis of the anti-angiogenic polyketide (-)-borrelidin under asymmetric catalytic control
Madduri, Ashoka V. R.,Minnaard, Adriaan J.
supporting information; experimental part, p. 11726 - 11731 (2010/11/18)
Borrelidin (1) is a polyketide that possesses extremely potent antiangiogenesis activity. This paper describes its formal total synthesis by the most efficient route to date. This modular approach takes optimal benefit of asymmetric catalysis and permits the synthesis of analogues; in addition, the high yields and selectivities obtained eliminate the need for separation of stereoisomers. The upper half of borrelidin has been accessed by iterative copper-catalysed asymmetric conjugate addition of methylmagnesium bromide, whereas synthesis of the lower half of the molecule was achieved by relying on asymmetric hydrogenation and cross-methathesis as key steps.
Catalytic asymmetric synthesis of mycolipenic and mycolipanolic acid
Horst, Bjorn Ter,Van Wermeskerken, Jeroen,Feringa, Ben L.,Minnaard, Adriaan J.
supporting information; experimental part, p. 38 - 41 (2010/03/24)
The first asymmetric synthesis of mycolipenic acid and mycolipanolic acid by using an improved iterative procedure involving catalytic asymmetric conjugate addition of MeMgBr as the key step is described. Mycolipenic and mycolipanolic acid are obtained in 11 steps with perfect stereocontrol, and both acids are identical to their counterparts from natural sources.
Catalytic asymmetric synthesis of phthioceranic acid, a heptamethyl-branched acid from Mycobacterium tuberculosis
Ter Horst, Bjorn,Feringa, Ben L.,Minnaard, Adriaan J.
, p. 3013 - 3015 (2008/02/10)
The first total synthesis of phthioceranic acid (1) has been achieved by an iterative catalytic asymmetric 1,4-addition protocol. This method provides a robust and high-yielding route for the preparation of 1,3-oligomethyl (deoxypropionate) arrays. After the desired number of methyl groups has been introduced, these arrays can be further functionalized at both ends to polymethyl-substituted lipids such as phthioceranic acid, a heptamethyl-branched fatty acid from the virulence factor Sulfolipid-I (2), found in Mycobacterium tuberculosis.
