870-63-3Relevant articles and documents
Facile synthesis of deuterium-labelled geranylgeraniols
Totsuka, Yusuke,Ueda, Shota,Shinada, Tetsuro,Kuzuyama, Tomohisa
, p. 575 - 577 (2015)
Facile and stereoselective syntheses of three different kinds of deuterium-labelled geranylgeraniol analogs have been achieved. LiAlD4 is used as the deuterium source to ensure high deuterium incorporation. [8,8-d2]- and [9,9-d2]- geranylgeraniols have been prepared for the first time. [10-d]- geranylgeraniol was efficiently prepared with a high degree of deuterium incorporation.
Synthesis of a phosphoantigen prodrug that potently activates Vγ9Vδ2 T-lymphocytes
Hsiao, Chia-Hung Christine,Lin, Xiaochen,Barney, Rocky J.,Shippy, Rebekah R.,Li, Jin,Vinogradova, Olga,Wiemer, David F.,Wiemer, Andrew J.
, p. 945 - 954 (2014)
Phosphoantigen-sensitive Vγ9Vδ2 T cells are important responders to infections and malignancy. However, the mechanisms by which phosphoantigens stimulate Vγ9Vδ2 T cells are unclear. Here, we synthesized phosphoantigen prodrugs and used them to demonstrate that intracellular delivery of phosphoantigens is required for their activity. The pivaloyloxymethyl prodrug is the most potent phosphoantigen described to date, with stronger stimulation of Vγ9Vδ2 T cells from human peripheral blood and greater ability to induce lysis of Daudi lymphoma cells relative to the previously most potent compound, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP). We demonstrate high binding affinity between phosphoantigens and the intracellular region of butyrophilin 3A1 (BTN3A1), localized to the PRY/SPRY (B30.2) domain, but also affecting the membrane proximal region. Our findings promote a phosphoantigen prodrug approach for cancer immunotherapy and unravel fundamental aspects of the mechanisms of Vγ9Vδ2 T cell activation.
The Application of 1,2-Oxazinanes as Chiral Cyclic Weinreb Amide-Type Auxiliaries Leading to a Three-Component, One-Pot Reaction
F?hrmann, Jan,Hermann, Ludmila,Hilt, Gerhard
, (2021/12/17)
1,2-Oxazines were synthesised via a copper-catalysed aerobic acyl nitroso Diels-Alder reaction from 1,4-disubstituted 1,3-dienes and N-Boc-hydroxylamine. From this, 1,2-oxazinanes were obtained in a novel follow-up reaction path. The stability of several 1,2-oxazines and 1,2-oxazinanes towards organometallic compounds was tested to rate their operability as cyclic chiral Weinreb amide auxiliaries. 3,6-Di-tertbutyl-1,2-oxazinane gave the best results and was introduced as a chiral Weinreb amide-type auxiliary to yield chiral α-substituted ketones in a diastereomeric ratio of up to 98:2. The removal of the auxiliary can be performed with BuLi to form unsymmetrical α-chiral ketones. Thereafter, the chiral auxiliary can be re-isolated and purified by sublimation under vacuum.
Using Terpene Synthase Plasticity in Catalysis: On the Enzymatic Conversion of Synthetic Farnesyl Diphosphate Analogues
Hou, Anwei,Dickschat, Jeroen S.
supporting information, p. 15644 - 15649 (2021/10/04)
Four synthetic farnesyl diphosphate analogues were enzymatically converted with three bacterial sesquiterpene synthases, including β-himachalene synthase (HcS) and (Z)-γ-bisabolene synthase (BbS) from Cryptosporangium arvum, and germacrene A synthase (SmTS6) from Streptomyces mobaraensis. These enzyme reactions not only yielded several previously unknown compounds, showing that this approach opened the door to a new chemical space, but substrates with blocked or altered reactivities also gave interesting insights into the cyclisation mechanisms and the potential to catalyse reactions with different initial cyclisation modes.
Gold-Catalyzed Formal Hexadehydro-Diels-Alder/Carboalkoxylation Reaction Cascades
Wang, Hong-Fa,Guo, Lin-Na,Fan, Zhi-Bo,Tang, Tian-Hua,Zi, Weiwei
supporting information, p. 2676 - 2681 (2021/04/12)
A dual gold-catalyzed hexadehydro-Diels-Alder/carboalkoxylation cascade reaction is reported. In this transformation, the gold catalyst participated in the hexadehydro-Diels-Alder step, switching the mechanism from a radical type to a cationic one, and then the catalyst activated the resulting aryne to form an ortho-Au phenyl cation species, which underwent a carboalkoxylation rearrangement rather than the expected aryne-ene reaction.
A mild method for the replacement of a hydroxyl group by halogen: 3. the dichotomous behavior of α-haloenamines towards allylic and propargylic alcohols
Munyemana, Fran?ois,Patiny, Luc,Ghosez, Léon
, (2021/06/07)
A study of the deoxyhalogenation of allylic and propargylic alcohols with tetramethyl-α-halo-enamines is reported. Primary allylic and primary and secondary propargylic alcohols gave the corresponding halides in high yields. Secondary allylic and propargylic alcohols yielded the corresponding secondary halides but the reaction also produced some rearranged primary halides (I > Br > Cl). The reactions with tertiary allylic and tertiary propargylic alcohols gave several products and was therefore of little synthetic value. However, the addition of triethylamine to the reaction mixture or the use of lithium alkoxide instead of alcohol brought about a major change of the course of the reaction which led to amides carrying an allyl or an allenyl group at C2. This was shown to result from a Claisen-Eschenmoser rearrangement of an intermediate α-allyloxy- or propargyloxy-enamine.
METHODS OF SYNTHESIZING FARNESYL DIBENZODIAZEPINONES
-
Paragraph 0082-0083, (2021/12/08)
The present invention is directed to synthetic means for producing farnesyl dibenzodiazepinone compounds, including AMO-01.
Scalable synthesis of the aroma compounds d6-β-ionone and d6-β-cyclocitral for use as internal standards in stable isotope dilution assays
Mosaferi, Shabnam,Jelley, Rebecca E.,Fedrizzi, Bruno,Barker, David
supporting information, (2020/12/02)
C13 Norisoprenoids are important aroma compounds in wine, giving positive attributes to the overall wine aroma even when found at very low levels. β-Ionone is considered one of the most important aroma compounds giving violet, woody and raspberry aromas to wine, fruits and vegetables in which it is found. Due to its potent aroma at low levels, precise analytical methods are desired for its quantification. Stable isotope dilution assay (SIDA) is one of the most important of these methods but requires the use of isotopically labelled standards. Herein, we describe the scalable synthesis of d6-β-ionone and d6-β-cyclocitral, another aroma compound with smokey and fruity notes, starting from the relatively inexpensive deuterated starting material d6-acetone.
Nickel-Catalyzed Asymmetric Reductive 1,2-Carboamination of Unactivated Alkenes
He, Jun,Xue, Yuhang,Han, Bo,Zhang, Chunzhu,Wang, You,Zhu, Shaolin
supporting information, p. 2328 - 2332 (2020/01/08)
Starting from diverse alkene-tethered aryl iodides and O-benzoyl-hydroxylamines, the enantioselective reductive cross-electrophilic 1,2-carboamination of unactivated alkenes was achieved using a chiral pyrox/nickel complex as the catalyst. This mild, modular, and practical protocol provides rapid access to a variety of β-chiral amines with an enantioenriched aryl-substituted quaternary carbon center in good yields and with excellent enantioselectivities. This process reveals a complementary regioselectivity when compared to Pd and Cu catalysis.
Enzymatic Synthesis of Methylated Terpene Analogues Using the Plasticity of Bacterial Terpene Synthases
Dickschat, Jeroen S.,Hou, Anwei,Lauterbach, Lukas
supporting information, (2020/02/11)
Methylated analogues of isopentenyl diphosphate were synthesised and enzymatically incorporated into methylated terpenes. A detailed stereochemical analysis of the obtained products is presented. The methylated terpene precursors were also used in conjunction with various isotopic labellings to gain insights into the mechanisms of their enzymatic formation.
