CN117247338A - 一种N-氨基-α-氨基酸类化合物及其合成方法 - Google Patents

一种N-氨基-α-氨基酸类化合物及其合成方法 Download PDF

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CN117247338A
CN117247338A CN202210654549.7A CN202210654549A CN117247338A CN 117247338 A CN117247338 A CN 117247338A CN 202210654549 A CN202210654549 A CN 202210654549A CN 117247338 A CN117247338 A CN 117247338A
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余达刚
曹光梅
宋何鑫
胡鑫龙
周琦
廖黎丽
叶剑衡
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Sichuan University
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Abstract

本发明提供了一种N‑氨基‑α‑氨基酸类化合物及其合成方法，其合成方法为：将腙反应底物、光催化剂、还原剂和碱加入反应容器中，然后在CO2气氛下加入有机溶剂，于光照条件下，20～70℃下搅拌反应0.1～48h，然后对反应产物进行分离、纯化，得N‑氨基‑α‑氨基酸类化合物；该合成方法能够在温和反应条件下合成重要的N‑氨基‑α‑氨基酸类化合物，具有反应底物范围广、产率及区域选择性良好、原料廉价易得、产物易于衍生的特点，该合成方法可有效解决现有技术中合成α‑芳基取代的α‑氨基酸产物存在局限性和需要使用金属还原剂等问题。

Description

一种N-氨基-α-氨基酸类化合物及其合成方法
技术领域
本发明属于有机合成技术领域，具体涉及一种N-氨基-α-氨基酸类化合物及其合成方法。
背景技术
α-氨基酸是一类重要的化合物，是多肽和蛋白质的基本组成单元。熟知的天然α-氨基酸只有20种，其制备可以通过微生物发酵实现。由于天然α-氨基酸结构中仅有氨基、羧基、巯基等可修饰的基团，实现其结构多样化面临一定的挑战。另一方面，非天然氨基酸结构单元广泛存在于一些天然产物、生物活性分子和药物分子的合成前体。因此合成结构多样的非天然氨基酸具有重要意义。
另一方面，二氧化碳(CO2)是一种廉价易得、安全无毒、储量丰富的碳一资源，使其经历参与化学转化，合成高附加值的化学品，具有重要意义。由于α-氨基酸广泛存在于药物分子和天然产物中，其经典的Strecker合成方法需要使用剧毒的氰化物作羧基源，因此使用绿色的CO2作为羧基源，发展可供选择的高效合成α-氨基酸的新方法，具有重要应用前景。但是目前为止，以CO2作为羧基源合成α-氨基酸的报道主要基于光化学、电化学、金属化学或者碱促进体系下形成碳负离子中间体或者烷基金属物种捕获CO2的机制，存在底物范围窄，当量金属作为还原剂等缺点，因此亟需发展条件温和且高效的合成方法。
发明内容
针对现有技术中存在的上述问题，本发明提供一种N-氨基-α-氨基酸类化合物及其合成方法，该方法是基于腙的羧基化反应而进行的，该合成方法能够在温和反应条件下合成重要的N-氨基-α-氨基酸类化合物，该方法具有反应条件温和、反应底物适用范围广、化学选择性良好、原料廉价易得的特点；该合成方法可有效解决现有技术中合成α-芳基取代的α-氨基酸产物存在局限性和需要使用金属还原剂等问题。
为实现上述目的，本发明解决其技术问题所采用的技术方案是：
一种N-氨基-α-氨基酸类化合物的合成方法，包括以下步骤：将反应底物、光催化剂、还原剂和碱加入反应容器中，然后在CO2气氛下加入有机溶剂，于光照条件下，20～70℃下搅拌反应0.1～48h，然后对反应产物进行分离、纯化，得N-氨基-α-氨基酸类化合物；
所述反应底物的结构通式如式(I)所示：
其中，R1、R2均为氢原子、全碳烷基、含杂原子烷基、芳基或三氟甲基；R3为氢原子或全碳烷基；R4为叔丁氧羰基、苄基氧羰基、苯基、苯甲酰基或磺酰基。
进一步地，反应底物、光催化剂、固体还原剂和碱的摩尔比为1:(0.001～0.01):(1～3.5):(0.5～3)。
进一步地，反应底物的结构通式如下：
进一步地，光催化剂为D-A型光催化剂或有机金属光催化剂。
进一步地，还原剂包括甲酸盐、有机胺、硅烷和硫酚中的至少一种。
进一步地，甲酸盐为甲酸锂、甲酸钾、甲酸钠或甲酸铯；
有机胺包括二异丙基乙基胺、三乙胺、三乙基醇胺、二环己基甲胺、二环己基乙胺、1,8-二氮杂双环[5.4.0]十一碳-7-烯或1-苯基-3-甲基-5-吡唑啉酮。
进一步地，有机溶剂包括MeCN、DMF、DMAc、DMSO和NMP中的至少一种。
进一步地，碱包括碳酸盐、碳酸氢盐、氟化盐、烷氧基碱、磷酸盐、磷酸氢盐、羧酸盐和有机碱中的至少一种。
进一步地，反应容器中的反应压力为0.1～30倍大气压，光源的波长为300～560nm，光源的功率为1～100W，光源与反应容器之间的距离为0.1～10cm。
一种N-氨基-α-氨基酸类化合物，采用上述方法制备获得。
本发明所产生的有益效果为：
1、本申请中的N-氨基-α-氨基酸类化合物在可见光的催化作用下，以原料易得的腙作为反应底物，CO2作为羧酸来源，同时加入光催化剂、还原剂和碱，制备获得；该方法具有反应条件温和、反应底物适用范围广、化学选择性良好、原料廉价易得的特点。
2、本发明提供的合成方法对于芳香族腙和脂肪族腙合物均具有良好的反应性，具有反应底物适用范围广的优点，且在使用特定试剂的情况下，产物的产率较高。
3、本发明首次实现了可见光催化腙的羧基化反应，此反应在温和条件下高效地实现N-氨基-α-氨基酸类化合物的合成，产物易于衍生，具有广泛的应用前景。
附图说明
图1为本发明的反应机理图。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅用以解释本发明，并不用于限定本发明，即所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。
实施例1
一种N-氨基-α-氨基酸类化合物的合成方法，当反应底物为时，其合成反应式如式(1-1)所示，具体为：
其合成方法包括以下步骤：
将配有搅拌子的10ml Schlenk反应管在真空下加热干燥后，加入反应底物腙化合物(0.2mmol，1.0eq.)和光催化剂3DPAFIPN-tBu(1.9mg，0.002mmol，1.0mol％)，随后将反应管移至手套箱内，依次加入碱Cs2CO3(65.0mg，0.2mmol，1.0eq.)，然后使用反应管对应旋塞密封反应管，移出手套箱，用双排管将反应管抽置换为CO2氛围，重复3次，随后在CO2氛围下依次将反应底物腙化合物、多聚硅烷PMHS(30μL,0.5mmol,2.5eq.)，超干DMSO(1mL或2mL)加入反应管中，加料完毕后立刻密封该反应管，将反应管固定在油浴锅中(油浴预先加热至60℃)，将反应所用搅拌器转速调至800-1300r/min，使用30W蓝色LED灯(波长为420-480nm左右)，在0.5cm远处照射，并使用风扇散热，使反应温度维持在60℃，搅拌反应12小时后，向反应混合物加入2.5mL乙酸乙酯稀释，再加入2mL 2N盐酸，搅拌10分钟，随后，使用2.5mL乙酸乙酯萃取反应液直到薄层色谱法监测无产物剩余，合并有机相并使用旋蒸彻底除去残留溶剂，得到的粗产物使用柱色谱分离纯化，纯化条件为：使用石油醚:乙酸乙酯＝10:1～5:1(v:v)的混合溶剂冲洗除去杂质，石油醚:乙酸乙酯：冰乙酸＝5:1:0.1％～1:2:0.5％(v:v)的混合溶剂冲洗得到目标产物。具体反应产物及对应的产物分离收率结果如下：
上述结果中，分离收率右上方标记a的数据为将有机溶剂替换为2ml DMSO，其余反应条件保持不变时的数据。
以上实验结果表明，目前适用于非环状脂肪族腙、环状脂肪族腙、脂肪族醛腙均能以良好的收率得到目标产物，同时也适用于芳香族腙类底物。此外，烯基、三氟甲基等官能团能很好地兼容于该反应中，大位阻的腙反应效果良好。
基于上述记载，对于本领域技术人员来说，满足上述反应机理条件的反应底物均符合条件，具体而言，当将反应底物替换为本申请所记载的其他反应底物时，其余成分和反应条件不变，最终得到的产率与本申请技术方案的产率变化不大，对此申请人不再单独列举实施例进行说明。
实施例2
在实施例1操作过程保持不变的基础上，以叔丁氧羰基保护的2-十三烷酮腙作为反应底物，通过改变反应条件，考察各个因素对反应产率的影响，反应条件：底物(0.2mmol，1eq.)，3DPAFIPN-tBu(0.02mmol，1.0mol％，1.9mg)，PMHS(0.5mmol,30μL,2.5eq.)，Cs2CO3(0.2mmol,65.0mg,1.0eq.)，超干溶剂DMSO(2mL)，具体实验结果见下表：
反应过程如下所示：
表：以叔丁氧羰基保护的2-十三烷酮腙作为反应底物在不同反应条件下的产物收率
由上表数据结果看出，在本发明反应条件下产率高达86％。一系列控制实验表明，光照、光催化剂、CO2、还原剂对反应起到不可或缺的作用，缺少任意一项无法得到或只能得到痕量的目标产物。当使用其他种类的光催化剂、碱和有机溶剂时，产率大幅下降，主要为原料剩余增多。在氮气氛围下能检测到产物的原因可能是由于碳酸盐在质子存在下分解产生CO2作为羧基源。在无3DPAFIPN-tBu的情况依然能够产生一定的产物，推测原因可能是腙反应底物在碱性条件下可以发挥光催化剂的作用，促进反应正向进行；温度对该反应有较大影响。利用甲酸铯代替多聚硅烷和CO2，也能以不错收率得到目标产物，根据说明图显示的机理，CO2和硅烷可以原位产生甲酸盐中间体，印证了该结果的合理性。
基于上述记载，对于本领域技术人员来说，满足上述反应机理条件的反应光催化剂、还原剂、碱和有机溶剂均符合条件，具体而言，将光催化剂、还原剂、碱和有机溶剂替换为本申请所记载的其他种类时，其余成分和反应条件不变，最终得到的产率与本申请技术方案的产率变化不大，对此申请人不再单独列举实施例进行说明。
另外，在现有实验研究结果的基础上，发明人提出反应机理，如图1所示。首先，含N-H键的底物腙在碱性条件下产生氮负离子中间体，随后与激发态光敏剂发生单电子转移(SET)过程得到还原态光敏剂与氮自由基中间体。另一方面，体系中多聚硅烷与CO2在碱性条件下原位产生甲酸盐中间体，通过氮自由基物种攫取甲酸盐的氢原子产生CO2自由基阴离子物种和底物腙，随后CO2自由基阴离子进攻腙的碳氮双键产生新的氮自由基物种，该物种与还原态光敏剂通过单电子转移(SET)过程被还原氮负离子，最后经过酸化处理得到目标产物。
对本发明所制得的产物进行了核磁共振和质谱表征分析。核磁和质谱表征数据结果与所得产物一致。具体表征数据如下：
2-(2-叔丁氧羰基肼基)-2-甲基十三酸
1H NMR(400MHz,DMSO-d6)δ7.71(s,1H),1.38(s,11H),1.24(s,18H),1.10(s,3H),0.90–0.81(m,3H).13C NMR(101MHz,DMSO-d6)δ176.84,156.94,78.83,64.09,36.70,31.79,29.98,29.53,29.49,29.42,29.20,28.54,23.81,22.57,21.31,14.37.HRMS(ESI-):calcdfor C19H37N2O4 -[M-H]-:357.2759,found 357.2761.
2-(2-苄氧羰基肼基)-2-甲基十三酸
(m,5H),5.12(s,2H),1.69–1.56(m,2H),1.37–1.25(m,21H),0.92(t,J＝6.7Hz,3H).13C NMR(101MHz,Methanol-d4)δ177.34,158.23,136.70,128.07,127.79,127.68,127.54,66.37,64.47,48.26,48.05,47.91,47.84,47.63,47.41,47.20,46.99,36.65,31.69,29.73,29.39,29.37,29.30,29.16,29.10,23.44,22.36,19.78,13.09.HRMS(ESI-):calcd forC22H35N2O4 -[M-H]-:391.2602,found 391.2605.
2-(2-苯甲酰基肼基)-2-甲基十三酸
7.90–7.78(m,2H),7.56–7.50(m,1H),7.49–7.42(m,2H),1.68–1.43(m,2H),1.22(s,21H),0.85(t,J＝6.8Hz,3H).13C NMR(101MHz,DMSO-d6)δ176.09,168.33,166.49,134.73,133.45,131.78,131.66,128.74,128.65,127.91,127.78,64.42,36.98,31.76,29.91,29.52,29.47,29.42,29.18,24.29,22.57,21.89,14.42.HRMS(ESI-):calcd forC21H33N2O3 -[M-H]-:361.2497,found 361.2497.
2-(2-叔丁氧羰基肼基)-2-甲基-4-苯基丁酸
1H),1.84–1.68(m,2H),1.40(s,9H),1.20(s,3H).13C NMR(101MHz,DMSO-d6)δ176.69,157.08,142.87,128.68,126.06,79.00,64.01,40.62,40.41,40.20,39.99,39.78,39.58,39.37,30.22,28.60,21.62.HRMS(ESI-):calcd for C16H23N2O4 -[M-H]-:307.1663,found307.1661.
4-(4-联苯基)-2-(2-叔丁氧羰基肼基)-2-甲基丁酸
7.38–7.32(m,1H),7.29(d,J＝8.0Hz,2H),2.79–2.67(m,1H),2.63–2.53(m,1H),1.91–1.70(m,2H),1.41(s,9H),1.21(s,3H).13C NMR(101MHz,DMSO-d6)δ176.66,157.13,142.17,140.59,138.06,129.33,129.31,127.58,127.02,126.94,79.04,64.02,38.50,29.86,28.62,21.65.HRMS(ESI-):calcd for C22H28N2NaO4 +[M+Na]+:407.1941,found 407.1938.
2-(2-叔丁氧羰基肼基)-4-(4-甲氧基苯基)-2-甲基丁酸
2.54(m,1H),2.49–2.40(m,1H),1.82–1.62(m,2H),1.40(s,9H),1.18(s,3H).13C NMR(101MHz,DMSO-d6)δ176.77,157.79,157.09,134.69,129.57,114.12,78.99,64.04,55.41,38.90,29.31,28.60,21.60.LRMS(ESI-):calcd for C17H25N2O4 -[M-H]-:337.18,found337.07.
2-(2-叔丁氧羰基肼基)-4-(4-甲氧基羰基苯基)-2-甲基丁酸
1H NMR(400MHz,DMSO-d6)δ8.01–7.72(m,3H),7.42–7.29(m,2H),3.83(s,3H),2.85–2.71(m,1H),2.68–2.56(m,1H),1.87–1.68(m,2H),1.40(s,9H),1.19(s,3H).13C NMR(101MHz,DMSO-d6)δ176.53,166.67,157.12,148.86,129.66,129.11,127.60,79.06,63.92,52.41,37.82,30.23,28.58,21.67.HRMS(ESI-):calcd for C18H25N2O6 -[M-H]-:365.1718,found 365.1717.
4-(1,3苯并二唑-5-基)-2-(2-叔丁氧羰基肼基)-2-甲基丁酸
1H),2.50–2.38(m,1H),1.83–1.56(m,2H),1.40(s,9H),1.17(s,3H).13C NMR(101MHz,DMSO-d6)δ176.70,157.10,147.59,145.55,136.71,121.33,109.17,108.45,100.99,79.02,63.96,38.80,29.93,28.59,21.63.HRMS(ESI-):calcd for C17H23N2O6 -[M-H]-:351.1562,found 351.1558.
2-(2-叔丁氧羰基肼基)-3-(3,4-二甲氧基苯基)-2-甲基丁酸
(m,1H),6.84–6.78(m,1H),6.77–6.70(m,1H),3.73(s,3H),3.71(s,3H),2.86–2.65(m,2H),1.39(s,9H),1.08(s,3H).13C NMR(101MHz,DMSO-d6)δ175.65,156.52,148.05,147.44,129.03,122.37,114.33,111.30,78.59,64.79,55.41,55.37,28.14,20.13.HRMS(ESI-):calcd for C17H25N2O6 -[M-H]-:353.1718,found 353.171.
2-苄基-2-(2-叔丁氧羰基肼基)-3-苯基丙酸
Methanol-d4)δ175.99,157.17,136.03,130.26,127.77,126.40,79.80,68.11,40.65,27.28.HRMS(ESI-):calcd for C21H25N2O4 -[M-H]-:369.1820,found 369.1818.
2-(2-叔丁氧羰基肼基)-2-乙基丁酸
1.39(s,9H),0.80(t,J＝7.4Hz,6H).13C NMR(101MHz,DMSO-d6)δ175.87,157.00,78.97,67.67,28.59,8.60.HRMS(ESI-):calcd for C11H21N2O4 -[M-H]-:245.1507,found 245.1506.
2-(2-叔丁氧羰基肼基)-2-三氟甲基丁酸
1.39(s,9H),0.88(t,J＝7.4Hz,3H).13C NMR(101MHz,DMSO-d6)δ168.81,157.07,125.51(q,J＝286.9Hz),79.59,69.72(q,J＝23.9Hz),28.48,22.26,8.19.19F NMR(376MHz,DMSO-d6)δ-71.74.HRMS(ESI-):calcd for C10H16F3N2O4 -[M-H]-:285.1068,found 285.1065.
2-(2-叔丁氧羰基肼基)-2-甲基5-己烯酸
4.94(m,2H),2.18–2.09(m,2H),1.77–1.68(m,2H),1.47(s,9H),1.28(s,3H).13C NMR(101MHz,Methanol-d4)δ177.13,157.56,138.08,113.65,79.58,64.21,35.60,27.86,27.26,19.80.HRMS(ESI-):calcd for C12H21N2O4 -[M-H]-:257.1507,found 257.1503.
2-(2-叔丁氧羰基肼基)-2-甲基丙酸
6H).13C NMR(101MHz,DMSO-d6)δ177.26,157.02,78.96,61.12,40.60,40.44,40.39,40.23,40.18,39.98,39.77,39.56,39.35,28.57,23.67.HRMS(ESI-):calcd for C9H17N2O4 -[M-H]-:217.1194,found 217.1198.
2-(2-叔丁氧羰基肼基)-2,3-二甲基丁酸
NMR(101MHz,DMSO-d6)δ177.01,156.90,78.84,67.02,33.49,28.58,17.65,17.46,16.63.HRMS(ESI-):calcd for C11H21N2O4 -[M-H]-:245.1507,found 241.1513.
2-(2-叔丁氧羰基肼基)-2-乙基-3-甲基丁酸
0.82(t,J＝7.4Hz,3H).13C NMR(101MHz,DMSO-d6)δ175.79,157.03,79.02,69.84,40.62,40.41,40.21,40.00,39.79,39.58,39.37,32.11,28.60,25.13,18.36,17.43,8.94.HRMS(ESI-):calcd for C12H23N2O4 -[M-H]-:259.1663,found 259.1666.
2-(2-叔丁氧羰基肼基)-2-环丙基丙酸
0.94(m,4H),0.43–0.24(m,4H).13C NMR(101MHz,DMSO-d6)δ175.89,156.59,78.46,63.20,28.12,18.40,17.31,0.86,0.68.HRMS(ESI-):calcd for C11H19N2O4 -[M-H]-:243.1350,found 243.1346.
2-(金刚烷基)-2-(2-叔丁氧羰基肼基)丙酸
DMSO-d6)δ176.01,157.03,78.80,69.90,40.40,40.19,39.99,39.78,39.57,37.72,37.01,36.57,28.58,28.49,14.79.HRMS(ESI-):calcd for C18H29N2O4 -[M-H]-:337.2133,found337.2135.
2-(2-叔丁氧羰基肼基)-2-异丙基-3-甲基丁酸
6H).13C NMR(101MHz,DMSO-d6)δ175.48,156.95,79.02,71.75,30.46,28.64,18.68,17.59.HRMS(ESI-):calcd for C13H15N2O4 -[M-H]-:273.1820,found 273.1824.
1-(2-叔丁氧羰基肼基)环戊基-1-甲酸
1.38(s,9H).13C NMR(101MHz,DMSO-d6)δ177.78,156.90,78.94,72.03,34.73,28.56,24.90.HRMS(ESI-):calcd for C11H19N2O4 -[M-H]-:243.1350,found 243.1351.
1-(2-叔丁氧羰基肼基)环己基-1-甲酸
1H NMR(400MHz,DMSO-d6)δ7.61(s,1H),1.69(d,J＝9.9Hz,4H),1.50–1.40(m,2H),1.38(s,9H),1.27(d,J＝23.4Hz,5H).13C NMR(101MHz,DMSO-d6)δ176.76,156.64,78.86,63.50,31.37,28.58,25.68,21.77.HRMS(ESI-):calcd for C12H21N2O4 -[M-H]-:257.1507,found 257.1508.
1-(2-叔丁氧羰基肼基)环庚基-1-甲酸
1.64–1.52(m,4H),1.50–1.34(m,15H).13C NMR(101MHz,DMSO-d6)δ177.89,156.74,78.87,67.19,34.24,30.51,28.56,22.83.HRMS(ESI-):calcd for C13H23N2O4 -[M-H]-:271.1663,found 271.1669.
1-(2-叔丁氧羰基肼基)环辛基-1-甲酸
177.51,157.42,79.55,67.58,48.24,48.03,47.88,47.81,47.60,47.39,47.17,46.96,28.62,27.97,27.23,24.78,21.87.HRMS(ESI-):calcd for C14H25N2O4 -[M-H]-:285.1820,found 285.1819.
1-(2-叔丁氧羰基肼基)环十二烷基-1-甲酸
176.45,156.67,78.96,66.66,28.57,28.48,26.57,26.09,22.65,22.24,18.90.HRMS(ESI-):calcd for C18H33N2O4 -[M-H]-:341.2446,found 341.2440.
4-(2-叔丁氧羰基肼基)四氢-2H-吡喃-4-甲酸
9H).13C NMR(101MHz,DMSO-d6)δ176.01,156.67,78.97,63.29,61.05,31.40,28.57.HRMS(ESI-):calcd for C11H19N2O5 -[M-H]-:259.1299,found 259.1296.
1-(叔丁氧羰基)-4-(2-叔丁氧羰基肼基)哌啶基-4-甲酸
18H).13C NMR(101MHz,DMSO-d6)δ176.08,156.62,154.40,78.99,61.75,30.56,28.57,28.55.HRMS(ESI-):calcd for C16H28N3O6 -[M-H]-:358.1984,found 358.1981.
1-(2-叔丁氧羰基肼基)-4-苯基环己基-1-甲酸
7.32–7.12(m,5H),2.47(d,J＝8.7Hz,1H),2.14–1.95(m,2H),1.86–1.64(m,3H),1.39(s,12H).13C NMR(101MHz,DMSO-d6)δ178.01,174.99,156.62,147.77,147.03,128.75,128.68,127.14,127.03,126.35,126.28,78.94,63.82,62.49,43.30,42.98,32.39,30.95,30.79,28.64,28.57.HRMS(ESI-):calcd for C18H25N2O4 -[M-H]-:333.1820,found 333.1818.
1-(2-叔丁氧羰基肼基)-2-甲基环己基-1-甲酸
1.95–1.81(m,1H),1.80–1.61(m,2H),1.61–1.39(m,3H),1.38(s,9H),1.33–1.18(m,3H),0.88(d,J＝6.9Hz,0.43H),0.79(d,J＝7.1Hz,2.57H).13C NMR(101MHz,DMSO-d6)13C NMR(101MHz,DMSO)δ177.84,175.91,156.57,78.93,66.63,36.97,30.27,29.20,28.59,28.55,25.67,21.69,20.52,16.38,16.31.HRMS(ESI-):calcd for C13H23N2O4 -[M-H]-:271.1663,found 271.1668.
2-(2-叔丁氧羰基肼基)-4-苯基丁酸
(m,1H),2.64–2.53(m,1H),1.92–1.70(m,2H),1.39(s,9H).13C NMR(101MHz,DMSO-d6)δ174.61,156.77,142.24,128.80,128.73,126.22,79.09,62.29,32.60,31.46,28.60.HRMS(ESI-):calcd for C15H21N2O4 -[M-H]-:293.1507,found 293.1509.
2-(2-叔丁氧羰基肼基)-3-乙基庚酸
MHz,DMSO-d6)δ174.88,156.75,78.98,64.59,41.61,29.75,29.55,29.47,29.40,28.59,23.23,22.84,22.77,14.41,14.37,12.29,12.02.HRMS(ESI-):calcd for C14H27N2O4 -[M-H]-:241.1976,found 241.1971.
2-(2-叔丁氧羰基肼基)-2-环己基乙酸
5H).13C NMR(101MHz,DMSO-d6)δ174.36,79.02,29.32,29.07,28.61,26.37,26.29.HRMS(ESI-):calcd for C13H23N2O4 -[M-H]-:271.1663,found 271.1667.
2-(2-苄氧羰基肼基)丁酸
5.04(s,2H),3.40(t,J＝5.9Hz,1H),1.63–1.50(m,2H),0.87(t,J＝7.4Hz,3H).13C NMR(101MHz,DMSO-d6)δ174.47,157.35,137.39,128.82,128.30,128.17,65.94,63.87,23.61,10.19.HRMS(ESI-):calcd for C12H18N2O4 +[M+H]+:253.1183,found 253.1179.
N-叔丁氧羰基氨基缬氨酸
NMR(101MHz,DMSO-d6)δ174.37,156.80,79.06,69.00,29.94,28.61,19.24,19.00.HRMS(ESI+):calcd for C10H20N2NaO4 +[M+Na]+:255.1315,found 255.1307.
N-苄氧羰基氨基缬氨酸
1H NMR(400MHz,DMSO-d6)δ8.64(s,1H),7.60–7.11(m,5H),5.04(s,2H),3.29–3.10(m,1H),1.98–1.82(m,1H),1.01–0.81(m,5H).13C NMR(101MHz,DMSO-d6)δ174.27,157.33,137.39,128.81,128.29,128.15,68.87,65.92,29.85,19.21,19.05.HRMS(ESI-):calcdfor C13H17N2O4 -[M-H]-:265.1194,found 265.1190.
2-(2-叔丁氧羰基肼基)-3,3-二甲基丁酸
79.03,73.06,33.80,28.61,27.17.HRMS(ESI-):calcd for C11H21N2O4 -[M-H]-:245.1507,found 245.1509.
虽然结合实施例对本发明的具体实施方式进行了详细地描述，但不应理解为对本专利的保护范围的限定。在权利要求书所描述的范围内，本领域技术人员不经创造性劳动即可作出的各种修改和变形仍属本专利的保护范围。

Claims (10)

1.一种N-氨基-α-氨基酸类化合物的合成方法，其特征在于，包括以下步骤：将反应底物、光催化剂、还原剂和碱加入反应容器中，然后在CO2气氛下加入有机溶剂，于光照条件下，20～70℃下搅拌反应0.1～48h，然后对反应产物进行分离、纯化，得N-氨基-α-氨基酸类化合物；
所述反应底物的结构通式如式(I)所示：
其中，R1、R2均为氢原子、全碳烷基、含杂原子烷基、芳基或三氟甲基；R3为氢原子或全碳烷基；R4为叔丁氧羰基、苄基氧羰基、苯基、苯甲酰基或磺酰基。
2.如权利要求1所述的N-氨基-α-氨基酸类化合物的合成方法，其特征在于，所述反应底物、光催化剂、固体还原剂和碱的摩尔比为1:(0.001～0.01):(1～3.5):(0.5～3)。
3.如权利要求1或2所述的N-氨基-α-氨基酸类化合物的合成方法，其特征在于，所述反应底物的结构通式如下：
4.如权利要求1所述的N-氨基-α-氨基酸类化合物的合成方法，其特征在于，所述光催化剂为D-A型光催化剂或有机金属光催化剂。
5.如权利要求1所述的N-氨基-α-氨基酸类化合物的合成方法，其特征在于，所述还原剂包括甲酸盐、有机胺、硅烷和硫酚中的至少一种。
6.如权利要求1所述的N-氨基-α-氨基酸类化合物的合成方法，其特征在于，所述甲酸盐为甲酸锂、甲酸钾、甲酸钠或甲酸铯；
所述有机胺包括二异丙基乙基胺、三乙胺、三乙基醇胺、二环己基甲胺、二环己基乙胺、1,8-二氮杂双环[5.4.0]十一碳-7-烯或1-苯基-3-甲基-5-吡唑啉酮。
7.如权利要求1所述的N-氨基-α-氨基酸类化合物的合成方法，其特征在于，所述有机溶剂包括MeCN、DMF、DMAc、DMSO和NMP中的至少一种。
8.如权利要求1所述的N-氨基-α-氨基酸类化合物的合成方法，其特征在于，所述碱包括碳酸盐、碳酸氢盐、氟化盐、烷氧基碱、磷酸盐、磷酸氢盐、羧酸盐和有机碱中的至少一种。
9.如权利要求1所述的N-氨基-α-氨基酸类化合物的合成方法，其特征在于，反应容器中的反应压力为0.1～30倍大气压，光源的波长为300～560nm，光源的功率为1～100W，光源与反应容器之间的距离为0.1～10cm。
10.一种N-氨基-α-氨基酸类化合物，其特征在于，采用权利要求1-9中任一项所述方法制备获得。
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