Total synthesis of the presumed amphidinolide A.
Total synthesis of the presumed amphidinolide A.
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推测的amphidinolide A的全合成。
DOI：
10.1002/1521-3773(20020201)41:3
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发表时间：
2002
影响因子：
--
通讯作者：
G. Pattenden
中科院分区：
文献类型：
--
作者：
H. Lam;G. Pattenden
（方案2）。[12通过使用DDQ [14]将8脱苄基化，然后将所得环状缩醛9与丙烷-1，3-二硫醇进行硫代缩醛化/开环反应，接着得到无环四醇10。在10中的羟基的甲硅烷基化之后，通过在丙酮水溶液中使用NBS除去产物11中的硫缩醛基团[15]，以显示醛12。12与相应的甲基酮13直接同系化，随后形成烯基三氟甲磺酸酯14，其在与衍生自（3-三甲基甲硅烷基丙-2-炔基）锂和碘化铜（i）的吉尔曼试剂反应后，以优异的产率得到双-TMS-炔15。通过NBS和AgNO3的作用将15中的炔TMS保护基交换为溴化物后，[16]钯催化的氢化锡烷基化[17]最终得到（E，E）-双烯基锡烷3，产率为83%。如方案3所示，从前述二醇17开始合成醛6，其是精制成4所需的。[18]因此，将17保护为其双-TBS醚18，然后将烯烃氧化裂解，得到醛19。19与Schenmoser × s盐[19]反应，得到α，β-不饱和醛20，在Lucche条件下还原，然后将所得烯丙醇21乙酰化，得到22。通过使用CSA选择性地除去22中的伯TBS醚基，从而得到醇23，其中沿着12%的回收的22，其可以循环。最后，用TPAP/NMO氧化23，[20]得到醛6。手性苯并噻唑基砜7（其是偶联至醛6所需的）由已知的酰化恶唑烷酮24 [21]制备（方案4）。以91 ∶ 9的非对映体选择性对衍生自24的烯醇化钠进行甲基化，纯化后得到非对映体纯的烷基化产物25，产率为76%。[22]减少方案2.试剂和条件：a）、（三甲基甲硅烷基）乙炔，nBuLi，Et2O，08 C 3RT，15 min，然后MgBr 2，RT，15 min，然后5，MgBr 2，CH308 C 3RT，1 h; B）DDQ，CH2Cl2/H2O（19：1），Δ，24 h; c）丙烷-1，3-二硫醇，BF 3/OEt2，CH2Cl2，08 C，4 h; d）TESOTf，2，6-二甲基吡啶，CH2Cl2，08 C，5 h; e）NBS，2，6-二甲基吡啶，丙酮/H2O（9：1），RT，40 min; f）MeMgBr，CH2Cl2，CH2788 C，15 min; g）Dess ± Martin过碘烷，NaHCO3，CH2Cl2，RT，35 min; h）KHMDS，PhNTf2，THF，CH278 308 C，3 h; i）LiCu（CH2C CTMS）2，THF，Na2O8C 3RT，12 h; j）NBS，AgNO3，丙酮，RT，10 h; k）Bu3SnH，Pd（PPh3）4，THF，RT，4 h。DDQ 2，3-二氯-5，6-二氰基-1，4-苯醌，TESOTf三乙基甲硅烷基三氟甲磺酸酯，NBS N-溴代琥珀酰亚胺，HMDS双（三甲基甲硅烷基）-酰胺。
(Scheme 2).[12, 13] Debenzylation of 8 by using DDQ,[14] followed by a thioacetalization/ring-opening reaction of the resulting cyclic acetal 9 with propane-1, 3-dithiol next led to the acyclic tetraol 10. After silylation of the hydroxy groups in 10, the thioacetal group in the product 11 was removed by using NBS in aqueous acetone [15] to reveal aldehyde 12. A straightforward homologation of 12 to the corresponding methyl ketone 13 was followed by the formation of alkenyl triflate 14, which upon reaction with the Gilman reagent derived from (3-trimethylsilylprop-2-ynyl) lithium and copper (i) iodide, gave the bis-TMS-alkyne 15 in excellent yield. After exchanging the alkyne TMS protecting groups in 15 for bromides by the action of NBS and AgNO3,[16] palladiumcatalyzed hydrostannylation [17] of the resulting bis-bromoalkyne 16 finally gave (E, E)-bis-alkenyl stannane 3 in 83% yield. Aldehyde 6, which is required for elaboration into 4, was synthesized as shown in Scheme 3 starting from the previously described diol 17.[18] Thus, protection of 17 as its bis-TBS ether 18, followed by oxidative cleavage of the alkene gave aldehyde 19. Reaction of 19 with Eschenmoser× s salt [19] next gave α, β-unsaturated aldehyde 20, which upon reduction under Luche conditions followed by acetylation of the resulting allylic alcohol 21 gave 22. The primary TBS ether group in 22 was removed selectively by using CSA, thus leading to alcohol 23, along with 12% of recovered 22, which could be recycled. Finally, oxidation of 23 with TPAP/NMO,[20] gave aldehyde 6. The chiral benzothiazolyl sulfone 7, which is required for coupling to aldehyde 6, was prepared from the known acylated oxazolidinone 24 [21](Scheme 4). Methylation of the sodium enolate derived from 24 proceeded with 91: 9 diastereoselectivity and gave, after purification, the diastereomerically pure alkylated product 25 in 76% yield.[22] ReductiveScheme 2. Reagents and conditions: a)(trimethylsilyl) acetylene, nBuLi, Et2O, 08C 3RT, 15 min, then MgBr2, RT, 15 min, then 5, MgBr2, À308C 3RT, 1 h; b) DDQ, CH2Cl2/H2O (19: 1), Δ, 24 h; c) propane-1, 3-dithiol, BF3¥ OEt2, CH2Cl2, 08C, 4 h; d) TESOTf, 2, 6-lutidine, CH2Cl2, 08C, 5 h; e) NBS, 2, 6-lutidine, acetone/H2O (9: 1), RT, 40 min; f) MeMgBr, CH2Cl2, À788C, 15 min; g) Dess±Martin periodinane, NaHCO3, CH2Cl2, RT, 35 min; h) KHMDS, PhNTf2, THF, À78 308C, 3 h; i) LiCu (CH2C CTMS) 2, THF, À208C 3RT, 12 h; j) NBS, AgNO3, acetone, RT, 10 h; k) Bu3SnH, Pd (PPh3) 4, THF, RT, 4 h. DDQ 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone, TESOTf triethylsilyl trifluoromethanesulfonate, NBS N-bromosuccinimide, HMDS bis (trimethylsilyl)-amide.