Synthesis of [13]-membered macrocyclic stevastelins via a transesterification reaction as the key step: total synthesis of stevastelin C3

A new synthesis of stevastelin C3 (3), a [13]-membered ring component of the stevastelin family, whose structure was recently revised, is reported. Initially, a macrolactonization approach was attempted to generate the [13]-membered macrolactone but this met with failure, so a translactonization reaction was tried to obtain the targeted stevastelin C3 (3) from the corresponding [15]-membered ring counterpart. Unfortunately, this strategy did not prove successful, and, consequently, we opted to undertake a transesterification reaction from 23, as a means to accommodate the requisite aminoacid moiety at the correct position, to obtain 24. From 24, and through intermediates 25-28, the acyclic precursor of the [13]-membered ring macrolactone, compound 30, was efficiently prepared. By utilizing the synthetic course developed by Chida, we took 30 forward and completed the total synthesis of stevastelin C3 (3).     

A convergent synthesis of the immunosuppressant FTY720 employing aqueous Wittig chemistry

A short, convergent synthesis of the immunosuppressant FTY720 is described involving the use of 4-hydroxymethylbenzaldehyde as a pivotal intermediate. A double Wittig strategy was developed to connect this dual-functional aldehyde with an alkyl-tether and to a readily available TRIS-derivative leading to an efficient synthesis of the target molecule.     

Total synthesis of mycestericin A

The first total synthesis of mycestericin A (1) starting from tartrates is described. The Overman rearrangement of an allylic trichloroacetimidate generated a tetra-substituted carbon with nitrogen, and subsequent stereoselective transformations afforded the highly functionalized vinyl iodide. The cross-coupling of the vinyl iodide with a chiral organozinc species under Negishi conditions, followed by deprotection, completed the total synthesis of 1.     

小肽免疫抑制剂的活性研究

用标准的Fmoc保护氨基酸Nα氨基的固相法合成了6肽Ac-XCSSXX-NH₂(-CSS-为保守序列,该设计合成的6肽是从若干单克隆中挑选出与IL-2结合力最高的),经HPLC纯化,并通过MS检测.分别以ConA诱导的淋巴细胞转化实验和IL-2诱导的淋巴母细胞转化实验为体外模型,以大鼠肝脏移植为体内模型,观察小肽对移植排斥的影响.在ConA诱导的淋转实验中,加入小肽(250～31.25μg/mL)对淋转反应有明显的抑制作用(P?0.01),在终浓度为31.25μg/mL时,抑制率达到最高.IL-2诱导的淋转实验得到与上述相符的结果,从而进一步表明:小肽是通过抑制IL-2和IL-2R的结合从而实现其免疫抑制作用的.在大鼠肝脏移植模型中:给术后大鼠注射小肽共5d(10mg/kg)可明显延长进行肝移植后大鼠的存活时间.     

Studies on the total synthesis of sanglifehrin A: stereoselective synthesis of the C(29)-C(39) fragment

A highly stereoselective synthesis of the C(29)-C(39) fragment of the potent immunosuppressant sanglifehrin A has been accomplished by a sequence involving 16 steps (18% overall yield) from N-propionyloxazolidinone 9. Key steps are a diastereoselective hydroboration, and a diastereoselective epoxidation of an allylic alcohol followed by a 1,5-anti boron-mediated aldol reaction of methyl ketone 4 with chiral aldehyde 5.     

The first total synthesis of lymphostin

Lymphostin (1), a novel immunosuppressant, has been synthesized from tryptophan through six kinds of regioselectively oxidative reactions.     

Studies directed towards the synthesis of antascomicin A: stereoselective synthesis of the C22-C34 fragment of the molecule

A stereoselective synthesis of the C22-C34 fragment of the non-immunosuppressive immunophilin-binding natural product, antascomicin A was achieved using d-quinic acid as the starting material and highly stereoselective aldol reactions were employed, as key steps, to build the remaining stereocentres at C23, C26 and C27.     

Synthesis and Immunosuppressive Activity of Amino Alcohol Containing Coumarin and Benzothiophene

A series of amino alcohol derivatives containing coumarin and benzothiophene moieties was synthesized with 5-bromosalicylaldehyde and 5-bromo-2-thiophenecarboxaldehyde as starting materials, 6-substituted-3-chroma- none and 4,5-dihydrobenzo[b]-thiophen-5(4H)-one as intermediates and Suzuki reaction and spiro-hydantoin hydrolysis as key steps. The structures of key intermediate and target compounds were confirmed by ¹H NMR, ¹³C NMR, IR and HRMS. Their characterization as sphingosine 1-phosphate(S1P) receptor agonists was reported.     

Synthesis and Immunosuppressive Activity of New Amino Alcohol Derivatives(Ⅰ)

A series of new amino alcohol derivatives was synthesized and evaluated for their immunosuppressive activity on mouse peripheral blood lymphocytes.The structures were confirmed by means of 1H NMR,13C NMR,IR and MS.Most of the compounds display moderate to potent inhibitory activity.Compound 9d shows the most activity among them that are expected as a powerful candidate for safer immunosuppressant for organ transplantations and the treatment of autoimmune diseases.     

Studies directed towards the synthesis of antascomicin A: stereoselective synthesis of the C1-C21 fragment of the molecule

A stereoselective synthesis of the C1-C21 fragment of the non-immunosuppressive immunophilin-binding natural product, antascomicin A was achieved using, as key steps, highly stereoselective Aldol reactions to build the C1-C17 fragment and a Nozaki-Hiyama-Kishi reaction to couple it with the remaining C18-C21 moiety.