CN112321475B - 一种γ-氨基酸类似物及其合成方法 - Google Patents

一种γ-氨基酸类似物及其合成方法 Download PDF

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CN112321475B
CN112321475B CN202011267379.4A CN202011267379A CN112321475B CN 112321475 B CN112321475 B CN 112321475B CN 202011267379 A CN202011267379 A CN 202011267379A CN 112321475 B CN112321475 B CN 112321475B
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余达刚
廖黎丽
曹光梅
蒋元旭
靳兴浩
胡鑫龙
柯杰森
孙国权
贵永远
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Sichuan University
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Abstract

本发明公开了一种γ‑氨基酸类似物及其合成方法，方法包括如下步骤：在干燥的反应管中加入光敏剂、碱、羧酸，再在保护气体的气氛下加入溶剂和反应底物，在可见光照射下进行反应，原料反应完后，对反应所得混合物进行酸化淬灭处理，分离纯化，即得产物γ‑氨基酸类似物；光敏剂包括Ir[dF(CF3)(ppy)]2(dtbbpy)·PF6、Ir(ppy)2(dbbpy)·PF6、4CzIPN，碱为氟化铯、碳酸铯或氟化钾；添加剂为分子筛；反应底物为烯类化合物。本发明在可见光诱导、保护气体气氛下高效高选择性地合成γ‑氨基酸类似物；本发明方案的反应条件温和，反应底物选择性广，且放大至克级规模。

Description

一种γ-氨基酸类似物及其合成方法
技术领域
本发明属于有机合成技术领域，具体涉及一种γ-氨基酸类似物及其合成方法。
背景技术
γ-氨基酸是一类重要的氨基酸。以γ-氨基丁酸为例，它是哺乳动物中枢神经系统中重要的抑制性神经递质，γ-氨基丁酸在大脑中的水平异常及γ-氨基丁酸受体功能障碍与多种神经和精神疾病有关。γ-氨基丁酸转氨酶在动物大脑内不断代谢γ-氨基丁酸,当降低到一定值时就会导致癫痫等疾病。而具有良好脂溶性，生理活性的γ-氨基丁酸类似物更是存在于许多药物分子中，最近几十年以来，以巴氯酚为代表的一系列γ-氨基丁酸类药物发展空前迅速，种类繁多而且不断有新的衍生物作为新药出现，表明氨基丁酸类药物市场前景广阔。但是文献报道得较多的γ-氨基丁酸类似物合成路线中，步骤繁琐、部分反应条件苛刻、底物来源不易，产物类型往往较为单一。
其传统合成方法主要有四类：一是α,β-不饱和硝基化合物或者羰基化合物为原料经Michael加成、氧化、还原等步骤制备；二是手性原料经手性反应立体选择性的获得特定构型的γ-氨基酸衍生物；三是复合酶催化一锅法合成γ-氨基酸衍生物；四是通过可见光催化下烯烃的氢烷基化反应制备γ-氨基酸类似物的方法。上述方法中，除了酶催化法和可见光催化法之外，其余方法都存在反应步骤繁琐、步骤经济性、原子经济性低、部分反应条件苛刻的问题；另外，酶催化法尚未得到工业应用；而现阶段的可见光催化法则需要反应底物上已预先引入羰基或者氨基，增加了底物的制作步骤。因此，其传统合成方法具有一定的局限性。研究新的、高效的合成γ-氨基丁酸药物的方法具有重要意义，如直接通过烯烃上同时引入氨基和羧基基团的策略。而同时，若能将光源这一清洁能源应用于γ-氨基酸类似物的合成中，无疑将会进一步符合绿色化学的合成理念。
另外，羧酸类是一类常见的，稳定的，商业易得的化合物，其可替代敏感且昂贵的金属试剂,因此被广泛应用于过渡金属催化的偶联反应中。除了研究充分的过渡金属催化的芳基羧酸脱羧反应外，烷基羧酸的自由基型脱羧反应也引起了广泛的关注。最近在光催化方面的重大进展更是为实现烷基和芳基羧酸的新型脱羧反应提供了强大的工具。通常在此类过程中，化学计量的二氧化碳(CO2)作为废弃物被释放出来，而未被再利用。这导致较低的原子经济性和大规模反应的潜在安全问题。
由于CO2的大量排放，大气中CO2浓度持续增高，直接导致了全球气候日益变暖，海平面升高，生态环境恶化，自然灾害频发。因此，积极开展CO2减排和合理利用的基础性研究十分重要。如果能够实现其向具有重要价值的羧酸分子的高效转化，并实现其工业化大规模生产，不仅可以创造化工生产工业模式，降低生产成本，还将大大提高CO2资源的利用效率，为解决温室效应提供一种新的思路。目前化学家们已经实现了一些CO2的转化并且获得的一系列具有高附加值化学品。然而，对CO2的化学利用特别是实现其工业化的部分仅仅是冰山一角，其主要原因归结于CO2的热力学稳定性和动力学惰性。因此,探索高效的，新型的CO2的转化反应，推动CO2的资源化利用进程，这具有重要的学术价值和实际意义。因此如果羧酸类化合物通过脱羧释放出的CO2可以被进一步利用于构建重要的含羧基的化合物，那么该设想将代表着碳原子经济和可持续的过程。
因此，如何利用羧酸脱羧产生的低浓度CO2以形成碳碳键仍存在很大挑战；同时如何开发一种可以克服上述缺点的，通过原位产生CO2-再利用以合成γ-氨基酸类似物的方法，是本领域所亟需的。
发明内容
本发明的目的在于，针对上述现有合成技术的缺点，提供一种γ-氨基酸类似物及其合成方法，该方法具有产率高、反应条件温和、反应试剂毒性低、成本低等优点。
本发明采用的技术方案如下：
一种γ-氨基酸类似物的合成方法，包括如下步骤：
S1：将光敏剂、碱与α-氨基酸或肽类混合，在保护气体的气氛下再加入溶剂和反应底物，得反应液；
S2：将S1所得反应液置于距可见光光源2-5cm处，室温下搅拌反应5-15h后用淬灭剂淬灭反应，旋干溶剂，得粗产物；
S3：通过快速柱层析纯化S2所得粗产物，即得γ-氨基酸类似物。进一步地，反应底物为烯类化合物，结构式如下式(I)所示，
Figure BDA0002776589840000021
其中，R1和R2为氢、烷基、芳基或吸电性官能团；R3为氢或甲基。
进一步地，所述吸电性官能团包括：
Figure BDA0002776589840000031
进一步，光敏剂为Ir类光敏剂，包括Ir[dF(CF3)(ppy)]2(dtbbpy)·PF6、Ir(ppy)2(dbbpy)·PF6、4CzIPN。
进一步，碱为氟化铯、叔丁醇钠、叔丁醇钾、叔丁醇锂、碳酸钾或碳酸铯。
进一步，在光敏剂、碱与α-氨基酸或肽类混合后再加入添加剂分子筛。加入添加剂分子筛能够增加产率。
进一步，溶剂为DMF、DMA、NMP或DMSO。
进一步，α-氨基酸或肽类为N-Boc-Phe-OH、N-Boc-Val-OH、N-Boc-Gly-Pro-OH、N-Boc-Ala-Pro-OH、N-Boc-Pro-Pro-OH、N-MeCO-Val-Pro-OH、N-Boc-Phe-Pro-OH、N-Boc-Lle-Pro-OH、N-Boc-Met-Pro-OH、N-Cbz-Pro-Val-Pro-OH或N-Cbz-Pro-OH。
进一步，淬灭剂为乙酸乙酯或盐酸水溶液。
进一步，光敏剂的用量为反应底物的0.01～10wt％；碱的添加量为反应底物的0.1～10倍当量；氨基酸或者肽类的添加量为反应底物的0.1～10倍当量。
进一步，保护气体为N2或CO2；可见光光源为30W的蓝色LED灯。
进一步，柱层析所用洗脱液为石油醚、乙酸乙酯和冰醋酸的混合物，混合物中石油醚与乙酸乙酯的体积比为10:1，冰醋酸的质量分数为0.1％。
本发明制备得到部分γ-氨基酸类似物如下：
Figure BDA0002776589840000041
本发明的反应原理如下：
Figure BDA0002776589840000051
光催化体系下，N-Cbz-Pro-OH先在碱的作用下形成羧酸盐,再与激发态的[Ir]光敏剂发生单电子转移过程脱羧生成α-氨基自由基和CO2，α-氨基自由基经由与烯烃的加成反应生成更加稳定的自由基物种，再将该物种还原为碳负离子进攻脱羧反应产生的CO2，合成γ-氨基丁酸衍生物。
本发明放大至克级规模，产率也不受影响，具体制备得到γ-氨基酸类似物的克级规模过程及其所得产品产率如下：
Figure BDA0002776589840000052
本发明的有益效果是：
本发明可以在可见光诱导下高效的合成γ-氨基酸类似物；本发明方案的反应条件温和，反应底物选择性广，且放大至克级规模，产率也基本不受影响；本发明克服了现有技术试剂毒性高、反应条件苛刻的缺陷，所用原料廉价易得。
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。
因此，以下对提供的本发明的实施例的详细描述并非旨在限制要求保护的本发明的范围，而是仅仅表示本发明的选定实施例。基于本发明的实施例，本领域技术人员在没有做出创造性劳动的前提下所获得的所有其他实施例，都属于本发明保护的范围。
需要说明的是，术语“第一”和“第二”等之类的关系术语仅仅用来将一个实体或者操作与另一个实体或操作区分开来，而不一定要求或者暗示这些实体或操作之间存在任何这种实际的关系或者顺序。而且，术语“包括”、“包含”或者其任何其他变体意在涵盖非排他性的包含，从而使得包括一系列要素的过程、方法、物品或者设备不仅包括那些要素，而且还包括没有明确列出的其他要素，或者是还包括为这种过程、方法、物品或者设备所固有的要素。在没有更多限制的情况下，由语句“包括一个……”限定的要素，并不排除在包括所述要素的过程、方法、物品或者设备中还存在另外的相同要素。
以下结合实施例对本发明的特征和性能作进一步的详细描述。
实施例1
本发明较佳的实施例提供一种γ-氨基酸类似物的合成方法，具体步骤如下：
Figure BDA0002776589840000061
S1：向干燥的Schlenk管(10mL)中，加入1(0.3mmol,1.0当量)，Ir[dF(CF3)(ppy)]2(dtbbpy)·PF6(3.3mg,0.003mmol,1mol％)，2a(97.3mg,0.39mmol,1.3当量)
S2：再加入Cs2CO3(147.0mg,0.45mmol,1.5当量)
S3：然后抽真空，置换氮气3次。随后在N2气氛下加入DMF(2.5mL)。
S4：将Schlenk管封好，在水浴中搅拌反应，用30W蓝色LED灯照射(3cm远，并有冷却风扇，使反应温度保持在25～30℃)8小时。
S5：反应结束后，用1ml 2N HCl(aq.)、2ml H2O淬灭，3ml EtOAc稀释，搅拌10min,EtOAc提取5次，组合后的有机相在真空中浓缩。
S6：最后利用硅胶柱层析(石油醚/乙酸乙酯/AcOH 10/1/0.1％)进行纯化，得到产品。
实施例2
本发明较佳的实施例提供一种γ-氨基酸类似物的合成方法，具体步骤如下：
Figure BDA0002776589840000071
S1：向干燥的Schlenk管(10mL)中，加入1a(0.3mmol,1.0当量)，Ir[dF(CF3)(ppy)]2(dtbbpy)·PF6(1.7mg,0.0015mmol,0.5mol％)，2(0.45mmol,1.5当量)
S2：再加入CsF(91.2mg,0.6mmol,2.0当量)
S3：然后抽真空，置换氮气3次。随后在N2气氛下加入DMA(3mL)。
S4：将Schlenk管封好，在水浴中搅拌反应，用30W蓝色LED灯照射(3cm远，并有冷却风扇，使反应温度保持在25～30℃)8小时。
S5：反应结束后，用1ml 2N HCl(aq.)、2ml H2O淬灭，3ml EtOAc稀释，搅拌10min,EtOAc提取5次，组合后的有机相在真空中浓缩。
S6：最后利用硅胶柱层析(石油醚/乙酸乙酯/AcOH 10/1/0.1％)进行纯化，得到产品。
实施例3
本发明较佳的实施例提供一种γ-氨基酸类似物的合成方法，具体步骤如下：
Figure BDA0002776589840000072
S1：向干燥的Schlenk管(10mL)中，加入1a(0.3mmol,1.0当量)，Ir[dF(CF3)(ppy)]2(dtbbpy)·PF6(1.7mg,0.0015mmol,0.5mol％)，2a(0.45mmol,1.5当量)。
S2：再加入CsF(137mg,0.9mmol,3.0当量)；再加入分子筛(200mg)。
S3：然后抽真空，置换氮气3次。随后在N2气氛下加入DMA(3mL)。
S4：将Schlenk管封好，在水浴中搅拌反应，用30W蓝色LED灯照射(3cm远，并有冷却风扇，使反应温度保持在25～30℃)8小时。
S5：反应结束后，用1ml 2N HCl(aq.)、2ml H2O淬灭，3ml EtOAc稀释，搅拌10min,EtOAc提取5次，组合后的有机相在真空中浓缩。
S6：最后利用硅胶柱层析(石油醚/乙酸乙酯/AcOH 10/1/0.1％)进行纯化，得到产品。
本发明实施例得到的产物及其产率如下所示：
Figure BDA0002776589840000081
Figure BDA0002776589840000091
实验例
在实施例2的基础上，在室温下一个大气压的N2气氛里以不同的反应条件进行反应，部分反应条件如表1所示：
表1二苯乙烯的反应条件及产率
Entry 与标准反应条件的改变 产率/3aa(％) 产率/3aa’(％)
1 无 96(81) (18)
2<sup>c</sup> 4CzIPN作为光敏剂 34 40
3<sup>c,d</sup> Ir(ppy)<sub>2</sub>(dtbbpy)·PF<sub>6</sub>作为光敏剂 78 39
4<sup>c,d</sup> fac-Ir(ppy)<sub>3</sub>作为光敏剂 n.d. n.d.
5 LiF作为碱 n.d. n.d.
6 KF作为碱 73 32
7<sup>c</sup> MeCN作为溶剂 13 37
8 N<sub>2</sub>(1atm)替换为CO<sub>2</sub>(1atm) (93) 7
9 无CsF n.d. n.d.
10 无光 n.d. n.d.
11 无光敏剂 n.d. n.d.
12 无光敏剂/光 n.d. n.d.
从表中可以看出，光敏剂、碱、可见光对于这种转化都是必不可少的。本发明成功地实现了以烯类化合物为起始物，以较好的产率得到了目标产物。本发明所合成的γ-氨基酸类似物的结构表征参数如下：
3-(1-(((苄氧基)羰基)吡咯烷-2-基)-2,2-二苯基丙酸(1):白色固体；1H NMR(400MHz,CDCl3)旋转异构混合物:δ9.63(s,1H),7.56–6.88(m,15H),5.01(dt,J＝25.1,10.6Hz,2H),3.68(s,0.5H),3.45–3.23(m,2.4H),3.12(d,J＝13.8Hz,0.5H),2.67(s,0.7H),2.39(t,J＝12.3Hz,0.4H),1.75(s,1H),1.58(s,1H),1.50–1.24(m,2H),0.99–0.85(m,0.6H)；13C NMR(101MHz,CDCl3)旋转异构混合物:δ178.58,177.86,155.08,154.95,143.42,143.04,142.58,141.92,136.62,129.17,128.85,128.45,128.06,128.00,127.90,127.14,66.98,59.11,58.46,56.01,55.46,46.22,40.87,30.05,29.75,29.37,23.57,22.76；HRMS(ESI+)[M+Na]+计算m/z为[C27H27NNaO4]+:452.1838,找到:452.1818。
3-(1-(叔丁氧基羰基)吡咯烷-2-基)-2,2-二苯基丙酸(2):白色固体；1H NMR(400MHz,CDCl3)旋转异构混合物:δ9.63(s,1H),7.56–6.88(m,15H),5.01(dt,J＝25.1,10.6Hz,2H),3.68(s,0.5H),3.45–3.23(m,2.4H),3.12(d,J＝13.8Hz,0.5H),2.67(s,0.7H),2.39(t,J＝12.3Hz,0.4H),1.75(s,1H),1.58(s,1H),1.50–1.24(m,2H),0.99–0.85(m,0.6H)；13C NMR(101MHz,CDCl3)旋转异构混合物:δ178.58,177.86,155.08,154.95,143.42,143.04,142.58,141.92,136.62,129.17,128.85,128.45,128.06,128.00,127.90,127.14,66.98,59.11,58.46,56.01,55.46,46.22,40.87,30.05,29.75,29.37,23.57,22.76；HRMS(ESI+)[M+Na]+计算m/z为[C27H27NNaO4]+:452.1838,找到:452.1818。
3-(1-乙酰基吡咯烷-2-基)-2,2-二苯基丙酸(3):白色固体1H NMR(400MHz,CDCl3)旋转异构混合物:δ7.48–7.44(m,1H),7.31–7.20(m,9H),3.95(s,1H),3.50–3.24(m,3H),2.10–2.05(m,3H),1.83–1.58(m,2.3H),1.33–1.05(m,1.7H),0.58–0.44(m,1H)；13C NMR(101MHz,DMSO-d6)旋转异构混合物:δ175.86,175.13,168.40,167.96,144.44,143.52,143.50,143.48,129.62,129.29,129.25,128.93,128.46,128.26,128.23,128.04,127.30,127.17,127.07,126.78,58.76,58.30,56.49,54.77,47.10,44.97,41.56,29.30,28.68,23.62,23.40,21.87,21.64；HRMS(ESI+)[M+Na]+计算m/z为[C21H23NNaO3]+:360.1576,找到:360.1556。
2-(3-甲氧基-3-氧代-2,2-二苯丙基)-1,1-二甲基吡咯烷-1-碘化物(4)+2-(2,2-二苯乙基)-1,1-二甲基吡咯烷-1-碘化铵(4'):黄色固体；1H NMR(400MHz,DMSO-d6):δ7.55–7.14(m,27.6H,3ad+3ad’),4.00(dd,J＝11.4,4.7Hz,1.76H,3ad’),3.69(s,3H,3ad),3.63–3.32(m,11H,3ad+3ad’),3.23–3.04(m,11H,3ad+3ad’),3.02–2.85(m,10H,3ad+3ad’),2.27–2.05(m,4H,3ad+3ad’),2.00–1.87(m,5H,3ad+3ad’),1.78–1.59(m,2H,3ad+3ad’)；13CNMR(101MHz,DMSO):δ173.45(3ad),145.13,143.08,142.22,129.35,129.30,129.07,128.93,128.79,128.55,128.00,127.85,127.22,126.91,73.81,72.61,66.12,65.38,58.72,53.16,50.08,49.80,47.95,44.40,43.74,37.53,32.90,27.76,27.15,19.27,19.17；LRMS(ESI+)[M-I]+计算m/z为3ad[C22H28NO2]+:338.21,找到:338.21,LRMS(ESI+)[M-I]+计算m/z为3ad’[C20H26N]+:280.20,找到:280.20；LRMS(ESI-)[I]-计算m/z为3ad and3ad’[I]-:126.91,找到:126.65。
3-(1-((苄氧基)羰基)哌啶-2-基)-2,2-二苯基丙酸(5):无色液体；1H NMR(400MHz,CDCl3)旋转异构混合物:δ9.53(s,1H),7.43–7.06(m,15H),5.12–4.70(m,2H),4.52–4.13(m,1H),4.07–3.73(m,1H),2.90(dd,J＝15.1,6.7Hz,2H),2.54(dd,J＝14.4,5.0Hz,1H),1.77–1.23(m,5H),0.98(d,J＝13.3Hz,1H)；13C NMR(101MHz,CDCl3)旋转异构混合物:δ178.44,156.74,155.26,142.38,136.53,129.25,128.78,128.49,128.38,127.97,127.88,127.83,127.00,67.55,67.05,59.17,54.27,48.22,41.93,39.81,38.44,30.39,29.74,26.60,25.47,24.72,20.86,20.74；HRMS(ESI+)[M+Na]+计算m/z为[C28H29NNaO4]+:466.1994,找到:466.1970。
3-(4-((苄氧基)羰基)吗啉-3-基)-2,2-二苯基丙酸(6):无色液体；1H NMR(400MHz,CDCl3)旋转异构混合物:δ9.48(s,1H),7.53–6.88(m,15H),5.21–4.70(m,2H),4.16(s,0.3H),3.99–3.58(m,2.7H),3.40–3.12(m,3H),2.94(dd,J＝14.3,5.5Hz,2H),2.83(dd,J＝14.4,6.0Hz,1H)；13C NMR(101MHz,CDCl3)旋转异构混合物:δ178.02,154.87,142.19,136.29,129.19,128.75,128.55,128.51,128.45,128.13,128.06,128.01,127.97,127.12,70.70,67.35,66.88,58.93,49.26,48.97,40.08,39.73,37.54；HRMS(ESI+)[M+Na]+计算m/z为[C27H27NNaO5]+:468.1787,找到:468.1764。
3-(4-(叔丁氧基羰基)吗啉-3-基)-2,2-二苯基丙酸(7):白色固体；1H NMR(400MHz,CDCl3)旋转异构混合物:δ7.41–7.20(m,10H),4.17–3.57(m,3H),3.33–3.00(m,3H),2.98–2.51(m,3H),1.29(d,J＝24.6Hz,9H)；13C NMR(101MHz,CDCl3)旋转异构混合物:δ177.99,154.02,142.46,141.81,129.29,128.83,128.11,128.08,127.13,80.17,69.94,66.96,59.08,49.47,37.34,28.28；HRMS(ESI+)[M+Na]+计算m/z为[C24H29NNaO5]+:434.1943,找到:434.1909。
3-((4S)-1-((苄氧基)羰基)-4-甲氧基吡咯烷-2-基)-2,2-二苯基丙酸(8)：无色液体；1H NMR(400MHz,CDCl3)旋转异构混合物:δ7.58–6.92(m,15H),5.10(s,2H),3.82–3.43(m,3.0H),3.31(dd,J＝12.1,4.5Hz,1H),3.10(d,J＝10.2Hz,3.0H),2.57–2.42(m,0.4H),2.36–2.23(m,0.6H),1.55(s,0.5H),1.27(d,J＝13.7Hz,2H),1.11(d,J＝13.1Hz,0.5H)；13CNMR(101MHz,CDCl3)旋转异构混合物:δ178.47,155.54,142.63,142.63,136.43,129.40,129.09,128.47,128.13,128.06,127.94,127.23,78.25,67.19,56.28,54.81,50.89,42.14,36.67；HRMS(ESI+)[M+Na]+计算m/z为[C28H29NNaO5]+:482.1943,找到:482.1905。非对映异构体通过LC MS分析确定为1.3。
3-(5-氧吡咯烷-2-基)-2,2-二苯基丙酸(9):白色固体；1H NMR(400MHz,DMSO-d6)δ12.90(s,1H),7.38–7.21(m,10H),7.12(s,1H),3.38(dt,J＝7.7,4.9Hz,1H),2.85(dd,J＝14.1,2.9Hz,1H),2.32(dd,J＝14.1,8.1Hz,1H),1.88(ddd,J＝9.4,6.8,3.3Hz,2H),1.32–1.21(m,1H),1.09–0.95(m,1H)；13C NMR(101MHz,DMSO-d6)δ176.46,175.47,143.66,142.58,129.33,129.13,128.48,128.43,127.36,127.22,58.90,52.00,44.76,30.45,28.61；HRMS(ESI+)[M+Na]+计算m/z为[C19H19NNaO3]+:332.1263,找到:332.1230。
4-((叔丁氧基羰基)氨基)-2,2,5-三苯基戊酸甲酯(10)：无色液体；1H NMR(400MHz,CDCl3)旋转异构混合物:δ7.30–6.92(m,15H),4.45(dd,J＝45.1,8.5Hz,1H),3.64(d,J＝11.6Hz,3H),3.37(t,J＝6.2Hz,0.75H),3.20(s,0.25H),2.83(dd,J＝13.3,5.4Hz,1H),2.63(ddd,J＝34.8,13.9,9.1Hz,2H),2.38(dd,J＝14.3,2.7Hz,0.74H),2.20–2.07(m,0.26H),1.33(d,J＝38.4Hz,9H)；13C NMR(101MHz,CDCl3)旋转异构混合物:δ174.98,154.52,143.27,142.01,138.25,129.57,129.30,129.02,128.50,128.25,128.17,127.93,127.13,126.91,126.20,78.67,59.00,52.46,49.40,42.77,41.56,28.47,28.20；HRMS(ESI+)[M+Na]+计算m/z为[C29H33NNaO4]+:482.2308,找到:482.2288。
5-苄基-3,3-二苯基吡咯烷酮-2-酮(11)：无色液体；1H NMR(400MHz,CDCl3)δ7.43–7.37(m,2H),7.36–7.21(m,11H),7.17(dd,J＝6.9,1.7Hz,2H),6.40(s,1H),3.82(tt,J＝8.4,5.7Hz,1H),3.01(dd,J＝12.9,5.6Hz,1H),2.88(dd,J＝13.4,5.8Hz,1H),2.77(dd,J＝13.4,8.0Hz,1H),2.51(dd,J＝13.0,8.8Hz,1H)；13C NMR(101MHz,CDCl3)δ177.62,144.04,141.52,137.30,128.99,128.84,128.49,128.24,128.01,127.76,127.10,126.94,126.69,58.03,52.51,43.79,42.48；HRMS(ESI+)[M+H]+计算m/z为[C23H22NO]+:328.1701,找到:328.1702。
4-((叔丁氧羰基)氨基)-5-甲基-2,2-二苯基己酸甲酯(12)：无色液体；1H NMR(400MHz,CDCl3)旋转异构混合物:δ7.41–7.15(m,10H),4.42(d,J＝9.1Hz,1H),3.69(s,3H),3.09(dtd,J＝6.5,4.3,2.0Hz,1H),2.73(dd,J＝13.9,10.8Hz,1H),2.26(dd,J＝13.9,2.6Hz,1H),1.66(tt,J＝6.9,3.3Hz,1H),1.42(s,9H),0.80(t,J＝6.9Hz,6H)；13C NMR(101MHz,CDCl3)旋转异构混合物:δ174.87,154.78,144.00,142.09,129.28,128.35,128.19,127.80,127.11,126.79,78.48,58.66,58.37,53.24,52.59,52.37,52.14,40.21,39.78,33.95,33.60,28.47,28.28,18.76,18.36,17.73,17.41；HRMS(ESI+)[M+Na]+计算m/z为[C25H33NNaO4]+:434.2307,找到:434.2318。
3-(1-((叔丁氧基羰基)甘氨酰基)吡咯烷-2-基)-2,2-二苯基丙酸(13)：无色液体；1H NMR(400MHz,CDCl3)旋转异构混合物:δ7.81–6.79(m,10H),5.63(d,J＝40.8Hz,1H),3.97–3.80(m,2H),3.48–3.31(m,2H),3.22(t,J＝8.1Hz,0.5H),3.07(d,J＝14.2Hz,0.5H),2.55(d,J＝22.9Hz,0.3H),2.31(d,J＝5.0Hz,0.7H),2.07–1.58(m,4H),1.54–1.38(m,10H)；13C NMR(101MHz,CDCl3)旋转异构混合物:δ176.27,167.72,156.01,155.90,143.42,142.80,129.92,129.25,129.11,128.92,128.73,128.18,128.04,127.94,127.22,127.06,126.98,79.74,79.66,59.18,58.41,56.36,55.74,46.02,45.66,45.49,43.18,43.02,29.71,29.33,28.38,28.37,28.36,27.22,25.94,24.12,23.72,22.70,20.91；HRMS(ESI+)[M+Na]+计算m/z为[C26H32N2NaO5]+:475.2209,找到:475.2189。
3-(1-((叔丁氧基羰基)-L-丙氨酰)吡咯烷-2-基)-2,2-二苯基丙酸(14)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ10.94(s,1H),7.50–7.11(m,10H),5.91(dd,J＝90.9,8.5Hz,1H),4.43(dt,J＝18.6,7.6Hz,0.7H),3.94(dt,J＝30.5,8.7Hz,0.7H),3.68–3.43(m,1H),3.42–3.22(m,1H),3.11(d,J＝13.8Hz,0.3H),3.02(d,J＝13.5Hz,0.3H),2.24(dt,J＝13.1,9.4Hz,1H),1.87–1.60(m,2H),1.42(d,J＝18.2Hz,9H),1.31–1.16(m,5H),0.79–0.63(m,1H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.38,172.36,171.98,155.61,155.48,155.10,143.66,143.27,143.12,129.41,129.32,128.87,128.12,128.02,127.95,127.91,126.99,126.90,79.74,79.50,59.12,58.89,56.56,56.07,48.19,47.76,46.63,46.42,40.54,40.16,29.71,29.33,28.39,23.92,23.59,18.55,17.81；HRMS(ESI+)[M+Na]+计算m/z为[C27H34N2NaO5]+:489.2366,找到:489.2303。非对映异构体通过1H NMR分析确定为1.1。
3-(1-((叔丁氧基羰基)-L-脯氨酰基)吡咯烷-2-基)-2,2-二苯基丙酸(15)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.91–6.65(m,10H),4.40(dt,J＝7.2,3.3Hz,0.6H),3.92(t,J＝8.4Hz,0.6H),3.71(d,J＝6.4Hz,0.3H),3.62–3.23(m,4H),3.07(d,J＝13.6Hz,0.3H),2.94(t,J＝12.6Hz,0.2H),2.38(d,J＝13.5Hz,0.2H),2.27–1.57(m,6.8H),1.37(dd,J＝63.1,31.2Hz,11.4H),0.74–0.46(m,0.6H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ175.76,172.43,154.89,154.60,144.30,143.71,142.41,129.40,129.25,128.72,128.62,128.04,127.95,127.87,127.67,127.30,127.06,126.83,126.67,80.10,79.81,59.65,59.51,59.34,58.53,58.12,58.04,57.91,57.73,56.72,46.99,46.85,46.68,45.24,41.29,30.16,29.71,29.67,29.33,29.20,29.10,28.59,28.52,28.47,28.47,28.45,28.32,24.49,24.37,24.04,23.86,23.55,23.27,22.70；HRMS(ESI+)[M+Na]+计算m/z为[C29H36N2NaO5]+:515.2522,找到:515.2498。非对映异构体通过1H NMR分析确定为1.1。
3-(1-((甲氧羰基)-L-戊基)吡咯烷-2-基)-2,2-二苯基丙酸(16)：无色液体；1HNMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.52–7.42(m,1H),7.42–7.39(m,1H),7.38–7.33(m,1H),7.29(dd,J＝7.4,4.7Hz,3H),7.26–7.16(m,4H),6.54(d,J＝9.5Hz,0.5H),6.26(d,J＝10.2Hz,0.5H),4.28–4.02(m,2H),3.78–3.66(m,2H),3.59–3.43(m,2H),3.36(td,J＝9.8,7.4Hz,0.5H),3.17–3.11(m,0.5H),2.19–1.92(m,2H),1.86–1.57(m,3H),1.28–1.09(m,1H),1.00–0.79(m,7H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.18,172.01,171.48,157.57,157.44,143.77,143.50,129.65,129.54,128.64,128.28,128.04,127.98,127.95,127.06,126.77,59.23,58.75,58.22,58.08,56.63,56.56,52.31,52.10,47.24,46.93,41.69,40.91,31.07,30.77,29.60,29.44,29.34,23.88,23.30,19.41,19.37,18.44,17.77；HRMS(ESI+)[M+H]+计算m/z为[C26H33N2O5]+:453.2389,找到:453.2331。非对映异构体通过1H NMR分析确定为1.0。
3-(1-((叔丁氧基羰基)-L-苯丙氨酰基)吡咯烷-2-基)-2,2-二苯基丙酸(17)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.52–6.97(m,15H),6.76–6.71(m,0.2H),6.28(d,J＝8.9Hz,0.3H),5.83(d,J＝8.7Hz,0.4H),5.67(d,J＝8.8Hz,0.1H),4.60(dtd,J＝47.4,9.1,6.2Hz,1H),3.89(dt,J＝39.1,8.8Hz,0.7H),3.46–3.28(m,1H),3.11–2.72(m,3.3H),2.69–2.36(m,0.8H),2.17(dd,J＝13.9,10.2Hz,0.5H),1.88(dd,J＝13.5,10.7Hz,0.4H),1.80–1.50(m,1H),1.48–1.32(m,10H),1.23–1.02(m,1H),0.94–0.82(m,0.5H),0.50(t,J＝8.2Hz,0.8H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.52,176.49,170.97,170.86,155.60,155.52,154.95,143.54,143.16,142.28,136.33,136.26,135.80,129.71,129.42,129.38,129.28,128.91,128.61,128.45,128.20,128.03,127.94,127.91,127.00,126.91,126.85,126.47,79.83,79.59,79.45,59.12,58.75,57.99,56.29,54.04,53.25,53.08,46.71,46.34,45.08,40.34,39.64,39.32,29.73,29.03,28.43,28.39,28.36,28.31,23.60,23.15；HRMS(ESI+)[M+Na]+计算m/z为[C33H38N2NaO5]+:565.2679,找到:565.2613.非对映异构体通过1H NMR分析确定为1.1(非对映异构体通过LC-MS分析确定为1.1)。
3-(1-((叔丁氧羰基)-L-异亮氨酰基)吡咯烷-2-基)-2,2-二苯基丙酸(18)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.86–6.80(m,10H),6.31(d,J＝9.3Hz,0.5H),5.54(d,J＝9.4Hz,0.3H),5.36(d,J＝11.1Hz,0.2H),4.28–4.06(m,1.3H),3.99(t,J＝8.9Hz,0.3H),3.83–3.64(m,0.7H),3.51–3.32(m,1H),3.17(dd,J＝19.8,13.5Hz,0.7H),2.83(dd,J＝24.0,12.8Hz,0.1H),2.13(t,J＝11.8Hz,1.3H),1.87–1.57(m,3.7H),1.55–1.23(m,10H),1.13(ddt,J＝31.0,14.3,6.6Hz,2H),0.86(dt,J＝28.7,7.3Hz,6H),0.50(t,J＝9.6Hz,0.9H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.03,172.41,172.01,156.22,156.12,143.94,143.73,143.39,129.61,129.38,128.68,128.34,128.11,128.02,127.93,127.90,127.14,127.03,126.86,126.72,79.76,79.26,59.51,58.70,56.88,56.71,56.56,47.39,47.03,41.34,40.63,37.64,37.12,29.81,29.66,29.34,28.39,28.37,28.32,24.71,24.30,23.96,23.44,15.53,15.49,11.15,11.06；HRMS(ESI+)[M+Na]+计算m/z为[C30H40N2NaO5]+:531.2835,找到:531.2810。非对映异构体通过1H NMR分析确定为1.1。
3-(1-((叔丁氧基羰基)-L-甲硫酰基)吡咯烷-2-基)-2,2-二苯基丙酸(19)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ11.47(s,1H),7.65–7.11(m,10H),6.19(d,J＝9.1Hz,0.4H),5.77(d,J＝9.0Hz,0.4H),4.72–4.29(m,1H),4.27–3.85(m,1H),3.75–3.33(m,2H),3.12(dd,J＝24.6,13.5Hz,1H),2.75(t,J＝6.4Hz,0.2H),2.51(dtd,J＝20.9,8.0,7.4,4.3Hz,1.8H),2.28–1.57(m,8H),1.43(d,J＝21.2Hz,9H),1.24–1.05(m,1H),0.57(t,J＝18.0Hz,1H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.17,175.89,171.68,171.25,155.97,155.85,143.74,143.50,143.31,129.51,129.37,128.72,128.55,128.07,128.01,127.97,127.95,127.09,126.89,126.84,79.90,79.58,59.24,58.84,56.74,56.45,51.41,51.05,46.94,46.65,41.25,40.69,32.59,31.99,30.37,30.24,29.71,29.61,29.42,28.38,28.36,28.33,23.89,23.57,15.73,15.65；HRMS(ESI+)[M+Na]+计算m/z为[C29H38N2NaO5S]+:549.2399,找到:549.2384。非对映异构体通过1H NMR分析确定为1.0。
3-(1-((((苄氧基)羰基)脯氨酰基-L-戊基)吡咯烷-2-基)-2,2-二苯基丙酸(20)：白色固体；1H NMR(400MHz,CDCl3)mixture of非对映异构与旋转异构混合物:δ7.86–7.43(m,2H),7.42–7.18(m,13H),5.29–4.94(m,2H),4.49(dt,J＝24.0,8.5Hz,1H),4.22–4.02(m,1.2H),4.00–3.33(m,5H),3.12(dd,J＝21.8,13.0Hz,0.8H),2.12–1.49(m,9H),1.31(d,J＝8.6Hz,1H),1.07–0.78(m,6H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.76,176.29,176.20,175.07,173.31,173.18,172.80,171.29,170.71,155.50,154.69,154.56,144.26,143.76,143.68,142.96,136.70,136.48,129.95,129.75,129.46,128.88,128.77,128.33,128.25,128.13,128.04,127.96,127.93,127.88,127.81,127.68,127.55,126.97,126.66,126.59,67.48,66.99,66.87,61.07,60.07,59.07,58.89,58.75,56.51,56.30,56.05,55.90,47.27,46.96,46.77,42.29,41.47,30.96,30.64,30.23,30.12,30.06,29.94,29.69,29.31,29.12,28.87,24.57,23.56,23.39,23.14,20.89,19.26,18.61,18.44,18.33,18.09；HRMS(ESI+)[M+Na]+计算m/z为[C37H43N3NaO6]+:648.3050,找到:648.3004。非对映异构体通过1H NMR分析确定为1.1。
3-((2S，3aS，6aS)-1-(((S)-1-乙氧基-1-氧基-4-苯基丁烷-2-基)-L-丙氨酸)八氢环戊[b]吡咯-2-基)-2,2-二苯基丙酸(21):白色固体；1H NMR(400MHz,CDCl3)mixture of非对映异构与旋转异构混合物:δ7.56–7.48(m,1H),7.44–7.07(m,14H),4.37–4.03(m,4H),3.89(b,0.7H),3.60(b,1H),3.12(d,J＝14.2Hz,0.7H),2.83–2.41(m,3.4H),2.37–1.82(m,3.8H),1.76–0.99(m,13.4H),0.74–0.39(m,1H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ175.39,173.45,144.30,143.23,140.66,140.04,129.23,128.81,128.50,128.47,128.43,128.38,128.15,128.11,127.93,127.19,127.06,126.90,126.22,63.54,63.30,61.92,61.51,59.74,59.34,57.98,52.77,41.81,39.87,39.44,34.58,34.43,33.99,33.92,32.03,31.74,29.71,29.65,29.13,24.17,23.76,14.26,14.22；HRMS(ESI+)[M+Na]+计算m/z为[C37H45N2O5]+:597.3328,found:597.3332.非对映异构体通过LC-MS分析确定为2.2。
2,2-二苯基-3-(四氢呋喃-2-基)丙酸(22)：白色固体；1H NMR(400MHz,CDCl3)δ7.39–7.16(m,10H),3.80(td,J＝7.8,6.1Hz,1H),3.70–3.51(m,2H),3.05(dd,J＝13.9,7.7Hz,1H),2.24(dd,J＝13.9,4.9Hz,1H),1.86(dddd,J＝13.6,11.8,7.9,5.9Hz,1H),1.77–1.56(m,2H),1.33(ddt,J＝12.7,8.5,6.6Hz,1H)；13C NMR(101MHz,CDCl3)δ178.62,144.02,141.83,129.51,128.45,128.10,127.86,127.11,126.80,76.04,67.41,58.84,44.14,31.96,25.69；HRMS(ESI+)[M+Na]+计算m/z为[C19H20NaO3]+:319.1310,找到:319.1281。
2,2-二苯基-3-(四氢-2H-吡喃-2-基)丙酸(23):无色液体；1H NMR(400MHz,CDCl3)δ7.34–7.19(m,10H),3.83(ddd,J＝11.3,4.4,2.2Hz,1H),3.07(td,J＝11.8,2.5Hz,1H),2.99–2.85(m,2H),2.26–2.16(m,1H),1.70(dt,J＝14.7,3.4Hz,1H),1.51(dt,J＝12.9,4.4Hz,1H),1.47–1.11(m,4H)；13C NMR(101MHz,CDCl3)δ177.78,144.52,141.96,129.39,128.40,127.98,127.80,126.98,126.75,75.03,68.29,59.03,44.44,32.03,25.39,23.29；HRMS(ESI+)[M+Na]+计算m/z为[C20H22NaO3]+:333.1467,找到:333.1431。
4,4-二甲基-2,2-二苯基戊酸(24)：无色固体；1H NMR(400MHz,CDCl3)δ7.55–7.47(m,4H),7.33–7.21(m,6H),2.66(s,2H),0.70(s,9H)；13C NMR(101MHz,CDCl3)δ180.36,144.44,129.19,127.76,126.67,57.34,50.10,31.42,30.47.LRMS(ESI+)[M-COOH]-计算m/z为[C18H21]-:237.16,找到:237.19。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-(甲硫基)苯基)-2-苯基丙酸(25)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ8.86(s,1H),7.66–6.82(m,19H),5.02(ddd,J＝33.1,15.0,7.5Hz,2H),3.85–3.69(m,0.5H),3.41(d,J＝9.5Hz,0.5H),3.38–3.10(m,2.4H),2.70(s,0.7H),2.36(d,J＝12.1Hz,0.5H),1.88–1.28(m,4H),0.95–0.86(m,0.5H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ178.42,177.72,155.07,140.50,139.68,136.65,129.61,129.28,128.83,128.83,128.80,128.49,128.11,128.04,127.92,127.37,127.04,126.61,126.61,67.02,58.97,56.10,55.50,46.26,41.26,40.84,30.11,29.78,29.40,23.53,22.81；HRMS(ESI+)[M+Na]+计算m/z为[C33H31NNaO4]+:528.2151,找到:528.2093。非对映异构体通过LC-MS分析确定为1.0。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-苯基-2-(对甲苯基)丙酸(26)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.53–7.13(m,10H),5.21–4.92(m,2H),3.69(br,0.5H),3.50–3.25(m,2H),3.12(br,J＝14.8Hz,0.5H),2.67(br,0.9H),2.31(m,3.1H),1.61(br,1H),1.37(d,J＝46.1Hz,1.5H),0.97(d,J＝14.3Hz,0.5H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ178.83,177.93,177.91,155.17,154.92,136.67,129.18,129.02,128.78,128.46,128.04,128.01,127.99,127.87,127.08,66.95,58.80,58.16,56.04,55.47,46.24,40.84,30.06,29.77,23.59,22.77,21.07,21.05；HRMS(ESI+)[M+Na]+计算m/z为[C28H29NNaO4]+:466.1994,找到:444.22。非对映异构体通过1H NMR分析确定为1.1。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-氟苯基)-2-苯基丙酸(27)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.56–6.70(m,14H),5.18–4.83(m,2H),3.69(d,J＝10.2Hz,0.5H),3.31(tdd,J＝11.0,8.8,5.2Hz,2H),3.13(d,J＝12.2Hz,0.5H),2.62(d,J＝16.7Hz,0.7H),2.42–2.27(m,0.6H),1.88–1.26(m,4H),0.95–0.80(m,0.7H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ178.32,177.95,177.62,177.29,163.00,160.54,155.27,154.82,154.63,138.44,136.50,136.45,131.24,130.79,128.93,128.48,128.19,128.09,127.87,127.25,114.94,114.73,67.08,67.04,58.82,58.63,56.01,55.84,55.27,46.21,41.16,30.29,29.75,29.36,23.56,22.74；19F NMR(376MHz,CDCl3)非对映异构与旋转异构混合物:δ-115.17,-115.41,-115.47,-115.63；HRMS(ESI+)[M+Na]+计算m/z为[C27H26FNNaO4]+:470.1744,找到:470.1721。非对映异构体通过LC-MS分析确定为1.2。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-甲氧基苯基)-2-苯基丙酸(28)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.51–6.97(m,12H),6.88–6.62(m,2H),5.18–4.96(m,2H),3.82–3.70(m,3H),3.51–3.23(m,2.4H),3.21–3.09(m,0.6H),2.64(d,J＝19.9Hz,0.8H),2.36–2.26(m,0.6H),1.70(d,J＝14.0Hz,1H),1.60(d,J＝10.4Hz,1H),1.41–1.25(m,2H),0.91–0.80(m,0.8H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ179.03,178.21,158.50,158.30,154.93,143.67,143.30,136.61,134.62,133.88,130.58,130.24,129.13,128.73,128.49,128.43,128.36,128.02,127.98,127.91,127.82,127.53,127.04,113.31,67.35,67.10,66.94,58.43,58.41,57.81,56.04,55.45,55.23,55.18,46.56,46.21,40.88,30.00,29.68,29.56,24.29,23.47,22.75；HRMS(ESI+)[M+Na]+计算m/z为[C28H29NNaO5]+:482.1944,找到:482.1918。非对映异构体通过LC-MS分析确定为1.2。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-苯氧基苯基)-2-苯基丙酸(29)：白色固体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.53–6.64(m,19H),5.04(dt,J＝34.9,14.7Hz,2H),3.73(s,0.5H),3.32(pt,J＝11.0,5.7Hz,2H),3.20–3.08(m,0.5H),2.66(s,0.7H),2.40–2.23(m,0.5H),1.66(d,J＝48.9Hz,2H),1.52–1.22(m,2H),0.95–0.78(m,0.8H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ177.81,177.48,177.39,156.81,156.34,154.89,136.58,136.53,130.47,129.79,129.78,129.02,128.47,128.13,128.05,128.03,127.15,123.49,119.21,117.92,67.07,66.99,58.69,56.09,56.01,55.38,46.24,41.38,41.20,40.89,30.45,23.59,22.76；HRMS(ESI+)[M+Na]+计算m/z为[C33H31NNaO5]+:544.2100,找到:544.2058。非对映异构体通过LC-MS分析确定为1.4。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-(甲硫基)苯基)-2-苯基丙酸(30)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.58(s,1H),7.59–6.90(m,14H),5.07(td,J＝30.7,29.2,16.8Hz,2H),3.75–3.25(m,3H),3.12(d,J＝14.0Hz,0.5H),2.67(d,J＝12.0Hz,0.8H),2.43(d,J＝2.6Hz,3.2H),1.74(s,1H),1.66–1.53(m,1H),1.54–1.26(m,2H),1.02–0.88(m,0.5H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ178.46,177.93,176.51,155.21,154.89,136.59,136.58,129.60,129.08,128.52,128.46,128.46,128.38,128.10,128.02,127.94,127.57,127.18,125.81,67.00,59.28,58.70,58.01,56.04,55.31,46.23,40.80,30.17,29.73,29.47,23.55,22.72,15.55；HRMS(ESI+)[M+Na]+计算m/z为[C28H29NNaO4S]+:498.1715,找到:498.1703。非对映异构体通过LC-MS分析确定为1.2。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-(戊-4-烯-1-基氧基)苯基)-2-苯基丙酸(31)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.39(s,1H),7.50–7.01(m,12H),6.88–6.58(m,2H),5.84(ddt,J＝16.9,10.4,6.6Hz,1H),5.05(d,J＝17.2Hz,2H),4.99(d,J＝10.3Hz,2H),3.92(s,2H),3.70(s,0.5H),3.49–3.22(m,2.5H),3.11(d,J＝13.6Hz,0.5H),2.64(s,0.6H),2.42–2.29(m,0.5H),2.22(q,J＝7.3Hz,2H),1.92–1.27(m,6H),0.91(dd,J＝17.3,7.2Hz,0.4H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ178.87,178.72,178.38,178.00,158.05,157.80,157.74,155.05,154.99,143.34,137.87,137.84,136.68,134.56,130.24,129.17,128.44,128.02,127.98,127.03,115.23,113.91,113.78,67.16,67.12,66.95,58.44,57.96,56.00,55.52,46.23,41.00,30.18,30.16,29.74,29.37,28.51,28.48,23.57,22.80；HRMS(ESI+)[M+Na]+计算m/z为[C32H35NNaO5]+:536.2413,找到:536.2398。非对映异构体通过1H NMR分析确定为1.1。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-(丁-2-炔-1-基氧基)苯基)-2-苯基丙酸(32)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.47–7.00(m,12H),6.82(d,J＝37.9Hz,2H),5.06(s,2H),4.60(d,J＝4.3Hz,2H),3.72(s,0.5H),3.53–3.27(m,2H),3.14(s,0.5H),2.64(d,J＝30.7Hz,0.7H),2.42–2.24(m,0.6H),1.85(q,J＝2.2Hz,3H),1.66(d,J＝53.0Hz,2H),1.29(s,2H),0.92–0.78(m,0.7H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ179.04,177.44,156.84,143.34,136.60,130.08,129.23,128.46,128.06,128.04,128.01,127.07,114.18,83.81,74.01,67.11,66.96,56.43,46.24,41.07,41.01,30.52,30.49,29.74,23.60,22.73,3.80；HRMS(ESI+)[M+Na]+计算m/z为[C31H31NNaO5]+:520.2100,找到:520.2084。非对映异构体通过1H NMR分析确定为1.2。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(3-氟苯基)-2-苯基丙酸(33)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.20(s,1H),7.52–6.82(m,14H),5.17–4.86(m,2H),3.70(d,J＝9.1Hz,0.5H),3.40–3.24(m,2H),3.08(t,J＝9.5Hz,0.5H),2.66(d,J＝11.9Hz,0.7H),2.44–2.28(m,0.5H),1.73(dt,J＝17.9,8.9Hz,1H),1.66–1.52(m,1H),1.49–1.24(m,2H),0.88(p,J＝6.6,4.7Hz,0.7H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ177.70,177.19,163.66,161.23,155.13,145.73,142.76,136.56,136.54,129.37,129.29,129.00,128.46,128.17,128.07,128.03,127.83,127.25,125.00,116.53,116.26,113.91,67.01,58.95,58.11,55.90,55.34,46.20,41.20,30.08,29.74,29.35,23.51,22.74；19F NMR(376MHz,CDCl3)非对映异构与旋转异构混合物:δ-112.54,-112.72,-112.75,-112.85；HRMS(ESI+)[M+Na]+计算m/z为[C27H26FNNaO4]+:470.1744,找到:470.1718。非对映异构体通过1H NMR分析确定为1.1。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-苯基-2-(3-(三氟甲基)苯基)丙酸(34)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.54(s,1H),7.92–6.81(m,14H),5.00(dd,J＝35.6,21.6Hz,2H),3.79–3.61(m,0.5H),3.39–3.23(m,2H),3.13(d,J＝13.8Hz,0.5H),2.68(s,0.7H),2.40(d,J＝12.2Hz,0.5H),1.76(h,J＝14.1,10.3Hz,1H),1.66–1.27(m,3H),0.89(dt,J＝14.6,7.8Hz,0.8H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ177.40,176.70,155.22,142.71,136.47,133.00,130.46,130.14,129.87,128.88,128.51,128.46,128.46,128.31,128.22,128.07,127.87,127.42,126.19,125.52,123.98,122.81,67.09,59.09,58.28,55.83,55.30,46.20,41.12,30.21,29.74,29.35,23.52,22.74；19F NMR(376MHz,CDCl3)非对映异构与旋转异构混合物:δ-62.32；HRMS(ESI+)[M+H]+计算m/z为[C27H27FNO4]+:498.1892,找到:498.1874。非对映异构体通过1H NMR分析确定为1.3。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(3-(甲氧基羰基)苯基)-2-苯基丙酸(35)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ10.01(s,1H),8.33–6.85(m,14H),5.20–4.84(m,2H),3.94–3.22(m,6H),3.16(t,J＝16.1Hz,0.5H),2.87–2.60(m,0.8H),2.42(dt,J＝23.8,11.5Hz,0.5H),1.91–1.23(m,4H),1.03–0.92(m,0.2H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ177.86,176.74,167.05,155.31,155.20,154.83,143.79,142.92,142.86,142.05,136.50,134.40,134.15,133.83,130.21,129.95,129.65,129.37,129.12,128.93,128.46,128.45,128.26,128.21,128.02,127.96,127.88,127.57,127.27,67.02,59.03,58.26,55.90,55.30,52.23,46.20,40.83,30.35,29.78,23.59,22.77；HRMS(ESI+)[M+Na]+计算m/z为[C29H29NNaO6]+:510.1893,找到:510.1857。非对映异构体通过1H NMR分析确定为1.2。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(3-(1-羧乙基)苯基)-2-苯基丙酸(36)：黄色固体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ10.40(s,2H),7.63–6.67(m,14H),5.15–4.85(m,2H),3.76–3.54(m,1.5H),3.29(dqt,J＝19.1,7.9,4.4Hz,2H),3.07(q,J＝13.2,12.5Hz,0.5H),2.82–2.30(m,1.5H),1.89–1.15(m,7H),1.05–0.89(m,0.5H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ180.27,171.62,155.06,142.77,139.46,136.60,129.17,128.44,128.04,127.97,127.82,127.18,66.94,59.19,55.89,55.50,46.17,46.04,45.40,45.20,40.64,40.55,29.80,29.35,23.49,22.80,18.37,17.79,17.59；HRMS(ESI+)[M+Na]+计算m/z为[C30H31NNaO6]+:524.2049,找到:524.2012。非对映异构体通过1H NMR分析确定为1.2。
3-(1-((苄氧基)羰基)哌啶-2-基)-2-(2-甲氧基苯基)-2-苯基丙酸(37)：无色液体；1H NMR(400MHz,CDCl3)δ8.07(d,J＝7.8Hz,1H),7.86–6.50(m,13H),5.12(d,J＝9.5Hz,2H),4.03–3.70(m,1H),3.50(d,J＝12.5Hz,3H),3.40–3.23(m,2H),3.17(d,J＝14.3Hz,0.6H),2.88(d,J＝14.3Hz,0.4H),2.63–2.30(m,1H),1.52(ddt,J＝48.4,16.6,8.7Hz,2H),1.10(dq,J＝54.6,7.4Hz,1H),0.90–0.65(m,0.5H),0.46(t,J＝8.4Hz,0.5H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ180.56,180.22,157.74,154.91,139.28,136.96,132.24,130.41,130.06,129.74,128.58,128.48,127.83,127.71,127.11,120.41,111.71,66.99,66.66,56.02,55.44,55.12,46.35,46.07,37.42,36.29,30.56,30.12,29.74,23.60,22.77；HRMS(ESI+)[M+Na]+计算m/z为[C28H29NNaO5]+:482.1944,找到:482.1882。非对映异构体通过LC-MS分析确定为2.0。
3-(1-(((苄氧基)羰基)吡咯烷-2-基)-2,2-双(4-氟苯基)丙酸(38)：无色液体；1HNMR(400MHz,CDCl3)旋转异构混合物:δ10.31(s,1H),7.59–6.58(m,13H),4.94(dq,J＝27.8,14.1,13.4Hz,2H),3.57(d,J＝9.0Hz,0.5H),3.23(q,J＝8.0,6.2Hz,2H),2.99(d,J＝13.8Hz,0.5H),2.54(d,J＝13.1Hz,0.8H),2.31–2.19(m,0.5H),1.80–1.19(m,4H),0.92–0.69(m,0.7H)；13C NMR(101MHz,CDCl3)旋转异构混合物:δ177.89,177.47,163.06,160.60,155.29,155.24,139.15,138.29,137.47,136.41,131.02,130.74,130.66,130.40,128.50,128.50,128.15,127.83,115.06,114.88,114.85,67.13,57.94,57.29,55.78,55.28,46.19,41.23,30.19,29.73,23.56,22.74；19F NMR(376MHz,CDCl3)旋转异构混合物:δ-114.82,-115.08,-115.13,-115.27；HRMS(ESI+)[M+H]+计算m/z为[C27H26F2NO4]+:466.1830,找到:466.1826。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(萘-2-基)-2-苯基丙酸(39)：白色固体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ8.92–6.82(m,17H),5.20–4.83(m,2H),3.85–3.73(m,0.4H),3.30(ddt,J＝18.6,14.9,5.6Hz,2.6H),2.79(s,0.5H),2.48(d,J＝13.6Hz,0.8H),1.88–1.22(m,4H),0.87(td,J＝13.6,7.8Hz,0.7H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ178.53,177.56,155.33,154.82,136.60,132.75,132.32,129.15,128.45,128.33,128.15,128.00,127.45,127.37,127.15,126.32,126.22,126.12,66.99,59.30,46.25,40.90,30.37,29.80,29.37,23.60；HRMS(ESI+)[M+H]+计算m/z为[C31H30NO4]+:480.2175,找到:480.2132。非对映异构体通过LC-MS分析确定为1.2。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(呋喃-3-基)-2-苯基丙酸(40)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.69(s,1H),7.76(d,J＝36.6Hz,0.6H),7.47–7.15(m,11H),7.10(s,0.4H),6.22(d,J＝69.7Hz,0.7H),5.70(s,0.3H),5.05(q,J＝8.9Hz,2H),4.01–3.59(m,1H),3.42–3.24(m,2H),2.97(dd,J＝29.6,13.7Hz,0.5H),2.81–2.51(m,1H),2.33–1.97(m,0.5H),1.89–1.37(m,3.7H),0.75–0.55(m,0.3H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ178.67,178.39,178.28,155.02,143.02,142.90,142.66,142.33,141.85,141.48,136.65,128.63,128.49,128.47,128.35,128.15,128.00,127.82,127.50,127.34,127.23,125.38,125.19,124.76,111.91,111.23,110.91,67.21,66.87,55.95,55.45,55.33,53.63,52.75,52.21,46.23,46.07,41.08,39.93,30.52,29.39,23.83,23.49,23.01；HRMS(ESI+)[M+Na]+计算m/z为[C25H25NNaO5]+:442.1630,找到:442.1607。非对映异构体通过LC-MS分析确定为1.7。
2-([1,1'-联苯]-4-基)-3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-甲基丙酸(41)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ10.43–8.82(m,1H),7.76–7.00(m,14H),5.24–4.79(m,2H),3.91(d,J＝41.2Hz,1H),3.32(p,J＝11.8Hz,2H),2.64–2.27(m,1H),2.26–1.97(m,1H),1.96–1.48(m,6H),1.31(d,J＝12.0Hz,0.5H),1.13–0.98(m,0.5H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ181.49,180.77,178.46,155.04,154.81,140.43,139.83,136.75,128.82,128.82,128.78,128.49,128.47,127.95,127.80,127.40,127.09,127.07,127.04,127.02,126.84,126.57,76.80,67.26,66.84,54.98,54.36,49.31,48.75,46.27,45.90,45.83,42.96,31.75,31.44,30.65,23.65,22.82,22.38,21.81；HRMS(ESI+)[M+Na]+计算m/z为[C28H29NNaO4]+:466.1995,找到:466.1988。非对映异构体通过LC-MS分析确定为1.6。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(3-苯氧基苯基)丙酸(42)：无色液体；1HNMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ10.43–8.82(m,1H),7.76–7.00(m,14H),5.24–4.79(m,2H),3.91(d,J＝41.2Hz,1H),3.32(p,J＝11.8Hz,2H),2.64–2.27(m,1H),2.26–1.97(m,1H),1.96–1.48(m,6H),1.31(d,J＝12.0Hz,0.5H),1.13–0.98(m,0.5H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ181.49,180.77,178.46,155.04,154.81,140.43,139.83,136.75,128.82,128.82,128.78,128.49,128.47,127.95,127.80,127.40,127.09,127.07,127.04,127.02,126.84,126.57,76.80,67.26,66.84,54.98,54.36,49.31,48.75,46.27,45.90,45.83,42.96,31.75,31.44,30.65,23.65,22.82,22.38,21.81；HRMS(ESI+)[M+Na]+计算m/z为[C27H28NO5]+:446.1967,找到:446.1979。非对映异构体通过LC-MS分析确定为1.1。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-氰基苯基)丙酸(43)：无色液体；1HNMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.66(s,1H),7.71–7.12(m,9H),5.23–4.95(m,2H),4.04–3.25(m,4H),2.64–1.95(m,2H),1.94–1.50(m,4H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.96,176.45,155.93,155.08,144.11,143.59,142.53,136.59,136.43,136.28,132.42,129.15,128.95,128.65,128.54,128.13,127.84,118.66,118.50,111.40,67.41,67.17,66.99,56.02,55.85,54.86,48.83,48.65,46.69,46.47,46.20,37.64,36.78,30.79,30.55,30.41,23.67,23.01；HRMS(ESI+)[M+Na]+计算m/z为[C22H22N2NaO4]+:401.1478,找到:401.1445。非对映异构体通过LC-MS分析确定为2.0。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-(三氟甲基)苯基)丙酸(44)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.66(s,1H),7.65–7.09(m,9H),5.25–4.94(m,2H),4.07–3.21(m,4H),2.42–1.52(m,6H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ177.69,177.21,155.80,155.10,142.15,141.17,136.51,136.31,129.87,129.54,128.67,128.65,128.56,128.50,128.28,128.05,127.92,127.81,127.53,125.63,125.59,125.55,125.52,67.32,67.07,55.86,54.88,48.61,48.45,46.63,46.41,38.14,37.52,36.73,31.25,30.44,30.38,29.71,29.38,23.65,22.98；19F NMR(376MHz,CDCl3)非对映异构与旋转异构混合物:δ-62.52,-62.57；HRMS(ESI+)[M+Na]+计算m/z为[C22H22F3NNaO4]+:444.1399,找到:444.1378。非对映异构体通过LC-MS分析确定为1.5。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(4-(甲氧基羰基)苯基)丙酸(45)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ10.85(s,1H),8.25–7.10(m,9H),5.21–4.99(m,2H),4.04–3.26(m,6.7H),2.67–2.52(m,0.3H),2.35–1.47(m,6H)；13CNMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ177.54,177.29,166.88,166.77,155.65,155.40,155.17,154.48,144.04,143.72,143.45,142.63,136.63,136.37,129.98,129.32,128.54,128.49,128.35,128.32,128.22,128.09,128.01,127.93,127.82,127.56,67.42,67.26,67.11,66.98,56.27,55.96,55.88,55.05,52.18,48.81,46.94,46.63,46.37,46.15,38.17,37.96,37.37,36.93,31.20,30.89,30.69,30.47,30.40,29.72,29.55,29.34,24.31,23.70,23.48,23.00,22.86；HRMS(ESI+)[M+Na]+计算m/z为[C25H25NNaO5]+:434.1580,找到:434.1559。非对映异构体通过LC-MS分析确定为1.7。
2-([1,1'-联苯]-4-基)-3-(1-((苄氧基)羰基)吡咯烷-2-基)丙酸(46)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.97(b,1H),7.75–7.19(m,4H),5.28–5.01(m,2H),4.15–3.57(m,2H),3.59–3.32(m,2H),2.76–2.61(m,0.6H),2.43–2.29(m,0.4H),2.24–2.06(m,0.5H),1.98–1.72(m,3.8H),1.67–1.56(m,0.7H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ178.50,178.32,177.96,155.21,140.67,140.43,136.75,128.78,128.78,128.76,128.60,128.51,128.10,127.85,127.40,127.07,67.15,66.97,66.86,56.42,56.01,55.14,48.52,48.35,46.63,46.38,46.13,38.08,37.50,36.98,31.19,30.73,30.45,29.73,23.72,22.91；HRMS(ESI+)[M+H]+计算m/z为[C27H28NO4]+:430.2018,找到:430.2016。非对映异构体通过LC-MS分析确定为1.2。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-3-正丁氧基-3-氧代丙酸(47)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.52(s,1H),7.55–6.92(m,5H),5.23–4.87(m,2H),4.19–3.83(m,3H),3.58–3.18(m,3H),2.28–1.74(m,5H),1.64–1.22(m,5H),0.82(q,J＝5.8,4.2Hz,3H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ172.27,172.25,169.41,169.09,156.44,155.34,136.64,136.47,136.27,128.47,128.41,128.21,128.06,127.91,127.88,67.41,67.17,66.96,65.51,56.01,55.78,55.55,55.40,46.50,46.25,34.37,33.59,31.03,30.39,29.65,29.28,23.61,23.46,22.82,18.95,13.63；HRMS(ESI+)[M+Na]+计算m/z为[C20H27NNaO6]+:400.1736,找到:400.1710。非对映异构体通过1H NMR分析确定为1.3。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-3-(叔丁氧基)-3-氧代丙酸(48)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.36(s,1H),7.47–7.27(m,5H),5.25–5.03(m,2H),4.18–3.93(m,1H),3.55–3.31(m,3H),2.34–2.06(m,1H),2.02–1.82(m,4H),1.73–1.63(m,1H),1.45(d,J＝10.0Hz,9H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ173.77,172.53,168.42,156.68,155.27,136.75,136.22,128.55,128.46,128.27,128.19,128.15,127.99,127.95,127.90,82.44,82.18,77.40,67.57,67.12,66.92,56.16,55.75,55.47,50.39,50.26,50.07,46.63,46.46,46.24,34.51,33.60,33.43,31.15,30.96,30.43,28.09,27.86,23.67,23.45,22.86；HRMS(ESI+)[M+Na]+计算m/z为[C20H27NNaO6]+:400.1736,找到:400.1705。非对映异构体通过1H NMR分析确定为1.5。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(3-氟苯基)-2-苯基丙酸(49)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.77(s,1H),7.48–7.15(m,5H),5.22–4.99(m,2H),4.03(d,J＝9.4Hz,1H),3.38(t,J＝6.2Hz,2H),2.53–2.12(m,1H),2.07–1.78(m,4H),1.70–1.61(m,1H),1.56–1.41(m,10H),1.37-1.31(m,2H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.51,176.03,175.85,171.98,155.01,154.87,136.64,136.49,128.42,127.97,127.78,82.40,82.08,67.16,66.88,54.50,53.92,53.10,52.85,52.70,45.98,45.83,39.32,31.31,31.02,27.73,23.64,22.79,21.19,20.66；HRMS(ESI+)[M+Na]+计算m/z为[C21H29NNaO6]+:414.1893,找到:414.1877。非对映异构体通过LC-MS分析确定为3.4。
2-((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-2-(叔丁氧基羰基)丁酸(50)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.34(s,1H),7.32(td,J＝15.2,13.8,8.8Hz,5H),5.11(tt,J＝26.8,13.1Hz,2H),4.11–3.80(m,1H),3.55–3.29(m,2H),2.33(ddd,J＝69.6,14.5,5.4Hz,1H),2.06–1.78(m,6H),1.66(q,J＝8.8,5.5Hz,1H),1.48(d,J＝29.5Hz,9H),0.85(dt,J＝47.1,7.5Hz,3H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.37,172.43,171.89,155.04,136.75,128.62,128.44,128.39,128.32,127.85,84.95,84.37,77.40,66.73,66.52,57.46,55.27,54.68,49.32,46.41,46.15,38.67,31.91,31.51,30.24,29.71,29.33,28.11,27.83,27.74,27.46,27.18,24.71,23.82,23.37,22.86,22.70,14.14；HRMS(ESI+)[M+Na]+计算m/z为[C22H31NNaO6]+:428.2049,找到:428.2031。非对映异构体通过1H NMR分析确定为1.4。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-3-(叔丁氧基)-2-环戊基-3-氧代丙酸(51)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.33(qd,J＝14.5,13.4,8.6Hz,5H),5.36–4.89(m,2H),4.12(tdt,J＝39.4,32.8,9.5Hz,1H),3.64–3.14(m,2H),2.44–1.17(m,24H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.37,172.43,171.89,155.04,136.75,128.62,128.44,128.39,128.32,127.85,84.95,84.37,77.40,66.73,66.52,57.46,55.27,54.68,49.32,46.41,46.15,38.67,31.91,31.51,30.24,29.71,29.33,28.11,27.83,27.74,27.46,27.18,24.71,23.82,23.37,22.86,22.70；HRMS(ESI+)[M+Na]+计算m/z为[C25H35NNaO6]+:468.2362,找到:468.2343。非对映异构体通过1H NMR分析确定为1.5。
2-((3-(叔丁氧基羰基)-2-氧四氢-2H-吡喃-3-基)甲基)吡咯烷-1-羧酸酯(52)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.41–7.22(m,5H),5.23–4.93(m,2H),4.37–3.88(m,3H),3.37(dd,J＝8.6,4.8Hz,2H),2.56–2.17(m,3H),2.09–1.77(m,5.3H),1.74–1.43(m,9H),1.36–1.22(m,1.7H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ170.62,170.32,169.56,155.06,136.90,128.83,128.42,128.21,127.80,127.62,82.98,68.73,67.37,66.64,53.86,53.49,53.14,46.14,45.34,40.86,39.83,31.84,31.37,27.76,26.66,26.40,23.37,22.80,20.53,20.06；HRMS(ESI+)[M+Na]+计算m/z为[C23H31NNaO6]+:440.2049,找到:440.2042。非对映异构体通过1H NMR分析确定为2.5。
3-(1-((苄氧基)羰基)吡咯烷-2-基)-2-(叔丁氧基羰基)-2-甲基丁酸(53)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.52–7.21(m,5H),5.24–5.02(m,2H),4.05(dq,J＝26.5,7.6,7.0Hz,1H),3.75–3.41(m,1H),3.38–3.14(m,1H),3.06–2.96(m,0.7H),2.49–2.30(m,0.3H),1.94–1.68(m,4H),1.55–1.25(m,12H),0.91(dt,J＝41.2,6.7Hz,3H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.25,175.97,175.93,172.11,171.68,155.85,155.29,136.92,128.77,128.45,128.44,128.01,127.97,127.88,127.64,82.67,67.40,66.78,58.09,56.95,46.39,46.22,42.71,29.71,29.33,27.75,26.55,24.67,23.38,18.72,16.41,13.52,10.86；HRMS(ESI+)[M+Na]+计算m/z为[C22H31NNaO6]+:428.2049,找到:428.2026。非对映异构体通过1H NMR分析确定为2：2.4:1:1。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-2-甲基-3-(((((3aaR，4S，7R)-八氢-1H-4,7-蛋氨酸-2-基)氧基)-3-氧代丙酸(54)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ8.71(s,1H),7.49–7.20(m,5H),5.10(pd,J＝14.3,11.9,3.9Hz,2H),4.56(d,J＝6.8Hz,1H),4.14–3.91(m,1H),3.40(tq,J＝13.6,8.1,6.6Hz,2H),2.42–2.19(m,1H),2.13–1.54(m,14H),1.49–1.14(m,6H),0.92(th,J＝12.4,6.4,4.9Hz,2H)；13CNMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.14,175.41,172.05,171.85,155.27,154.91,136.62,136.57,128.46,128.44,128.07,127.98,127.77,82.84,82.51,67.23,66.93,54.37,53.64,53.03,52.72,52.32,52.13,49.02,48.98,48.86,48.77,46.95,46.93,45.89,44.99,44.96,39.85,39.64,38.50,38.32,33.78,33.66,31.44,31.28,29.71,26.99,26.97,23.62,22.81,21.41,21.26,20.09,20.07,19.70,19.68,11.59,11.37；HRMS(ESI+)[M+Na]+计算m/z为[C27H35NNaO6]+:492.2362,找到:492.2345。非对映异构体通过LC-MS分析确定为1.7。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-3-(((((3R，9R，10S，13S，14S，17S)-17-((2S，5S，E)-5,6-二甲基庚-3-烯-2-基)-10,13-二甲基-2,3,4,9,10,11,12,13,14,15,16,17-十二烷基-1H-环戊[a]菲基-3-基)氧基)-2-甲基-3-氧代丙酸(55)：无色液体；1HNMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.90(s,1H),7.48–7.22(m,5H),5.10(qt,J＝12.9,7.8Hz,2H),4.75–4.46(m,1H),4.05(t,J＝6.3Hz,1H),3.38(q,J＝9.9,8.3Hz,2H),2.37(dq,J＝12.3,3.9Hz,1H),2.08–1.64(m,8H),1.56(d,J＝8.7Hz,3H),1.41–1.25(m,2H),1.09(qd,J＝17.0,14.8,6.4Hz,2H),1.01–0.72(m,9H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.18,175.42,172.05,171.86,155.27,154.92,136.62,136.46,128.46,128.44,128.07,127.99,127.77,82.84,82.51,67.23,66.93,54.37,53.63,53.03,52.72,52.32,49.02,48.98,48.86,48.76,46.95,46.93,45.89,44.99,44.95,39.64,38.50,38.32,33.78,33.66,31.43,29.71,29.33,26.98,23.61,22.82,21.40,21.25,20.09,20.07,19.70,19.68,11.59,11.37；HRMS(ESI+)[M+Na]+计算m/z为[C27H37NNaO6]+:494.2519,找到:494.2504。非对映异构体通过LC-MS分析确定为3.5。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-2-甲基-3-(((((3aaR，4S，7R)-八氢-1H-4,7-蛋氨酸-2-基)氧基)-3-氧代丙酸(56)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ8.71(s,1H),7.49–7.22(m,5H),5.22–5.00(m,2H),4.56(d,J＝6.9Hz,1H),4.05(td,J＝23.0,22.3,15.6Hz,1H),3.37(dt,J＝13.8,6.3Hz,2H),2.47–1.11(m,23H),0.91(dp,J＝19.3,7.4,6.5Hz,2H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.18,175.42,172.05,171.86,155.27,154.92,136.62,136.46,128.46,128.44,128.07,127.99,127.77,82.84,82.51,67.23,66.93,54.37,53.63,53.03,52.72,52.32,49.02,48.98,48.86,48.76,46.95,46.93,45.89,44.99,44.95,39.64,38.50,38.32,33.78,33.66,31.43,29.71,29.33,26.98,23.61,22.82,21.40,21.25,20.09,20.07,19.70,19.68,11.59,11.37；HRMS(ESI+)[M+Na]+计算m/z为[C27H37NNaO6]+:496.2675,找到:496.2679。非对映异构体通过LC-MS分析确定为1.5。
3-((((3s，5s，7s)-金刚烷-1-基)氧基)-2-((1-(((苄氧基)羰基)吡咯烷基-2-基)甲基)-2-甲基-3-氧代丙酸(57)：白色固体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.83(s,1H),7.51–7.18(m,5H),5.27–4.94(m,2H),4.22–3.85(m,1H),3.40(dd,J＝16.4,8.8Hz,2H),2.41–2.01(m,10H),2.01–1.74(m,4H),1.72–1.52(m,8H),1.37(s,1H),1.33(s,1H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.09,175.69,172.08,155.15,154.90,136.64,128.44,128.41,127.99,127.82,82.87,82.64,67.05,66.92,54.57,53.96,53.09,52.76,52.51,46.07,45.90,40.96,40.94,39.58,36.04,31.37,31.13,30.83,29.70,27.23,23.67,22.86,22.10,21.51；HRMS(ESI+)[M+Na]+计算m/z为[C27H35NNaO6]+:492.2362,找到:492.2335。非对映异构体通过LC-MS分析确定为3.6。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-2-甲基-3-((1-甲基环戊基氧基)-3-氧代丙酸(58)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ7.71–7.45(m,1H),7.32(dd,J＝13.9,5.3Hz,5H),5.21–5.00(m,2H),4.03(s,1H),3.37(d,J＝7.4Hz,2H),2.43–2.19(m,1H),2.10(d,J＝13.9Hz,2H),2.03–1.78(m,4H),1.74–1.47(m,11H),1.41–1.22(m,2H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.37,175.88,175.60,172.13,155.08,154.87,136.62,136.47,128.43,128.42,128.01,127.99,127.79,92.05,91.87,67.18,66.93,54.52,53.89,53.11,52.71,52.59,45.90,39.40,38.86,38.84,38.82,31.38,31.23,29.69,29.31,23.82,23.75,23.73,22.78,21.32,20.61；HRMS(ESI+)[M+Na]+计算m/z为[C23H31NNaO6]+:440.2049,找到:440.2037。非对映异构体通过LC-MS分析确定为4.3。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-2-甲基-3-氧代-3-((1-(丙-1-基-1-基)环己基)氧基)丙酸(59)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ9.48(s,1H),7.47–7.20(m,5H),5.20–4.99(m,2H),4.04(dt,J＝14.4,6.0Hz,1H),3.53–3.29(m,2H),2.45–2.20(m,1H),2.09–1.74(m,12H),1.56(d,J＝11.2Hz,5H),1.49–1.26(m,4H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ176.17,175.88,170.45,155.04,154.93,136.69,136.52,128.44,128.04,127.95,127.80,82.79,82.59,78.64,78.50,77.76,77.63,67.14,66.87,54.46,53.87,53.05,52.54,46.06,45.85,39.34,39.11,37.46,37.37,36.75,36.61,31.13,30.87,29.70,29.33,25.06,23.72,22.88,22.38,20.81,20.50,3.75,3.69；HRMS(ESI+)[M+Na]+计算m/z为[C26H33NNaO6]+:478.2206,找到:478.2179。非对映异构体通过LC-MS分析确定为2.2。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-2-甲基-3-((2-甲基丁-3-烯-2-基)氧基)-3-氧代丙酸(60)：无色液体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ8.71(s,1H),7.32(ddt,J＝12.3,8.1,3.5Hz,5H),6.04(dt,J＝17.5,12.1Hz,1H),5.38–4.99(m,4H),4.03(t,J＝6.8Hz,1H),3.37(q,J＝6.9Hz,2H),2.44–2.17(m,1H),2.07–1.78(m,4H),1.71–1.63(m,1H),1.52(d,J＝9.0Hz,7H),1.35(d,J＝25.7Hz,2H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ175.77,175.33,171.68,155.19,154.98,141.71,136.59,128.45,128.43,128.43,128.05,128.01,127.81,113.38,113.32,82.70,67.14,66.96,54.53,53.85,53.07,52.72,52.52,45.95,45.89,39.51,31.44,31.28,29.71,29.33,26.10,25.99,25.74,23.63,22.79,21.70,20.88,18.07；HRMS(ESI+)[M+Na]+计算m/z为[C22H29NNaO6]+:426.1893,找到:426.1875。非对映异构体通过LC-MS分析确定为2.8。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-3-((((((8R，9R，10S，13S，14R，17S)-10,13-二甲基-17-((S)-6-甲基庚-2-基)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-十四氢-1H-环戊[a]菲蒽-3-基)氧基)-2-甲基-3-氧代丙酸(61)：白色固体；1H NMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ8.02(s,1H),7.42–7.14(m,5H),5.49–5.25(m,1H),5.21–5.01(m,2H),4.83–4.44(m,1H),4.24–3.88(m,1H),3.37(dt,J＝14.6,7.0Hz,2H),2.42–2.17(m,3H),2.08–1.77(m,9H),1.72–1.22(m,15H),1.20–0.96(m,12H),0.95–0.81(m,10H),0.67(s,3H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ174.80,172.52,155.09,139.37,139.25,136.52,128.47,128.43,128.01,127.81,122.96,75.57,67.01,56.68,56.13,54.53,52.77,52.12,49.99,45.90,42.31,39.72,39.52,37.61,36.87,36.57,36.19,35.80,31.92,31.84,31.47,28.24,28.03,27.35,24.30,23.84,23.62,22.85,22.59,21.04,19.33,18.74,11.87；HRMS(ESI+)[M+Na]+计算m/z为[C44H65NNaO6]+:726.4710,找到:726.4690。非对映异构体通过1H NMR分析确定为1.1。
2-(((1-((苄氧基)羰基)吡咯烷-2-基)甲基)-3-(((((3R，9R，10S，13S，14S，17S)-17-((2S，5S，E)-5,6-二甲基庚-3-烯-2-基)-10,13-二甲基-2,3,4,9,10,11,12,13,14,15,16,17-十二烷基-1H-环戊[[a]菲基-3-基)氧基)-2-甲基-3-氧代丙酸酸(62)：白色固体；1HNMR(400MHz,CDCl3)非对映异构与旋转异构混合物:δ8.60(s,1H),7.40–7.28(m,5H),5.54(dt,J＝7.1,3.5Hz,1H),5.37(dt,J＝5.3,2.6Hz,1H),5.20(dd,J＝8.9,7.1Hz,2H),5.15–5.05(m,2H),4.71(t,J＝11.0Hz,1H),4.13–3.95(m,1H),3.39(d,J＝8.0Hz,2H),2.55–2.22(m,3H),2.10–1.81(m,12H),1.80–1.56(m,7H),1.50–1.21(m,10H),1.04(d,J＝6.7Hz,3H),0.92(d,J＝7.1Hz,6H),0.83(t,J＝6.5Hz,6H)；13C NMR(101MHz,CDCl3)非对映异构与旋转异构混合物:δ174.80,172.47,155.39,154.90,141.59,136.51,135.54,132.00,128.48,128.48,128.44,128.04,127.83,120.46,116.32,74.38,67.04,55.70,54.53,53.75,52.78,52.13,46.00,42.82,40.47,40.00,39.01,37.77,37.07,36.21,36.15,33.10,31.48,29.72,29.34,28.31,27.70,23.62,23.01,22.41,22.28,21.14,21.03,19.98,19.67,17.64,16.16,12.08；HRMS(ESI+)[M+Na]+计算m/z为[C45H63NNaO6]+:736.4553,找到:736.4528。非对映异构体通过1H NMR分析确定为1.3。
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 (6)

1.一种γ-氨基酸类似物的合成方法，其特征在于，包括如下步骤：
S1：将光敏剂、碱与α-氨基酸或肽类混合，在保护气体的气氛下再加入溶剂和反应底物，得反应液；所述保护气体为N2或CO2；所述反应底物为烯类化合物，结构式如下式(I)所示：
Figure 778668DEST_PATH_IMAGE002
其中，R1和R2为氢、烷基、芳基或吸电性官能团，所述吸电性官能团为：
Figure 226967DEST_PATH_IMAGE003
；R3为氢或甲基；
所述光敏剂为Ir[dF(CF3)(ppy)]2(dtbbpy)•PF6、Ir(ppy)2(dbbpy)·PF6或4CzIPN；
所述碱为氟化铯、叔丁醇钠、叔丁醇钾、叔丁醇锂、碳酸钾或碳酸铯；
所述α-氨基酸或肽类为N-Cbz-Pro-OH、N-Boc-Phe-OH、N-Boc-Val-OH、N-Boc-Gly-Pro-OH、N-Boc-Ala-Pro-OH、N-Boc-Pro-Pro-OH、N-MeCO-Val-Pro-OH、N-Boc-Phe-Pro-OH、N-Boc-Lle-Pro-OH、N-Boc-Met-Pro-OH或N-Cbz-Pro-Val-Pro-OH；
S2：将S1所得反应液置于距可见光光源2-5cm处，室温下搅拌反应5-15h后用淬灭剂淬灭反应，旋干溶剂，得粗产物；所述可见光光源为30W的蓝色LED灯；
S3：通过快速柱层析纯化S2所得粗产物，即得γ-氨基酸类似物；所述γ-氨基酸类似物的结构式如下：
Figure DEST_PATH_IMAGE005
Figure DEST_PATH_IMAGE007
。
2.根据权利要求1所述的γ-氨基酸类似物的合成方法，其特征在于：在光敏剂、碱与α-氨基酸或肽类混合后再加入添加剂分子筛。
3.根据权利要求1所述的γ-氨基酸类似物的合成方法，其特征在于：所述溶剂为DMF、DMA、NMP或DMSO。
4.根据权利要求1所述的γ-氨基酸类似物的合成方法，其特征在于：所述淬灭剂为乙酸乙酯或盐酸水溶液。
5.根据权利要求1所述的γ-氨基酸类似物的合成方法，其特征在于：所述光敏剂的用量为反应底物的0.01~10wt%；所述碱的添加量为反应底物的0.1~10倍当量；所述氨基酸或者肽类的添加量为反应底物的0.1~10倍当量。
6.根据权利要求1所述的γ-氨基酸类似物的合成方法，其特征在于，所述柱层析所用洗脱液为石油醚、乙酸乙酯和冰醋酸的混合物，混合物中石油醚与乙酸乙酯的体积比为10:1，冰醋酸的质量分数为0.1%。
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