CN103709101A - 一类renierramycin G的合成中间体及其制备方法 - Google Patents
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Abstract
本发明涉及一类具有通式(I)的新型双四氢异喹啉化合物(结构式如下)及其制备方法。通式(I)化合物是通过含四氢异喹啉单元的醛片段与三取代苯丙氨酯片段间的Pictet-Spengler环化反应一步制得的,所用的两个偶联片段均由廉价的L-酪氨酸高效合成。通式(I)化合物作为高级合成中间体,可用来方便、高产率地制备具有显著抗癌活性的(–)-renierramycin G等多种renieramycin型生物碱和类似物。基于通式(I)化合物为中间体的合成路线,总收率上较已有的(–)-renierramycin G的合成方法有明显提高,还具有原料便宜,条件温和,操作简便,灵活多用,易于工业化等优点,为合成各种renieramycin型生物碱和类似物提供了一种高效经济的方法。
Description
发明领域
本发明涉及一类(-)-renierramycin G的合成中间体及其制备方法。
发明背景
Renieramycins、saframycins和ecteinascidins等海洋双四氢异喹啉生物碱及其类似物,由于具有显著的抗肿瘤、抗菌等活性,在化学、生物学、医学等研究领域受到广泛关注。其中的ecteinascidin
743自2007年开始已率先在欧洲、韩国等成为治疗多种晚期软组织肿瘤的抗癌药物使用(药品名:Trabectedin;Yondelis)[Nat. Rev. Drug
Discovery 2009, 8, 69]。研究表明在抗肿瘤活性上,ecteinascidin
743比目前临床上广泛使用的喜树碱、紫杉醇、阿霉素、博来霉素、丝裂霉素C、顺铂及依托泊甙等著名抗癌药物高出1~3个数量级,且具有独特的多重作用机制。1992年从海绵Xestospongia caycedoi 得到的(-)-renierramycin
G,在结构上与此家族大多数成员的C21位存在
-氨基醇或氨基腈不同,其C21位为酰胺基团,代表了该生物碱家族的另一类型。虽然一般认为C21位-氨基醇和氨基腈基团的存在对于此类生物碱的活性至关重要,然而缺乏该官能团的renierramycin
G等生物碱却依然具有明显的抗癌活性 [Tetrahedron 2000, 56, 7305;J. Nat. Prod. 2000, 63, 793;Chem.
Pharm. Bull. 2007, 55, 81;Tetrahedron
2012, 68, 2759],因此此类化合物的抗癌作用机制还需进一步探明。但由于renieramycin
G等生物碱在自然界含量低,很难满足构效关系和活性药理研究等需要[Tetrahedron
2012, 68, 4166],发展经济实用的不对称合成方法对于其的发展十分重要。
2005年,Williams等首次完成了(-)-renieramycin
G的不对称合成[J. Am. Chem. Soc. 2005, 127, 12684],如反应式一所示,该路线主要特点是通过酰胺键将两个手性四取代苯丙氨酸衍生物1和2偶联起来,再来关C环和D环形成五环骨架:
反应式一
随后,Liu等也用类似的合成策略完成了(-)-
renieramycin G及类似物的合成[Tetrahedron 2009, 65, 5709; Tetrahedron
2012, 68, 2759],但两个偶联用的四取代苯丙氨酸片段是由较廉价的L-酪氨酸甲酯制备,成本上有较大较低。偶联产物3关上C和D环后经氢化脱溴等步骤得到五环中间体4。4不仅可方便地转化为(-)-
renieramycin G,而且可经还原后用于合成更多类型的此类生物碱(反应式二)。
反应式二
Zhu等则从丝氨酸衍生物出发,经过两个铜盐存在下环氮化合物与芳基格氏试剂反应和两个环化反应,得到双四氢异喹啉中间体6。6再通过关C环,氧化芳环成对醌等几步顺利得到(-)-renieramycin
G(反应式三)[Org. Lett. 2009, 11, 5558]。
以上这些不对称合成路线取得了较好的结果,但仍有一些地方存在不足。例如有的合成片段制备路线长,或需要制备多个合成片段;有些步骤产率不够理想;有些涉及一些较贵的试剂和原料;一些反应条件要求苛刻不易操作等。这些会导致合成成本上升,不易进行较大规模制备。发展更简洁廉价的方法来不对称合成双四氢异喹啉类生物碱及衍生物,对其应用前景至关重要。
发明目的
本发明提供了一类具有通式(I)的双四氢异喹啉化合物及其制备方法。以这类化合物作为高级中间体来不对称合成renieramycin G等生物碱及衍生物,在产率、成本等方面较以往合成路线有明显提高。
发明内容
本发明获得了一类具有通式(I)的双四氢异喹啉化合物及其合成方法,通式(I)化合物是通过化合物A与化合物B间的一个Pictet-Spengler环化反应来制备的,结构式及合成路线如下:
上面路线每个结构式中R1、R2、R3、R4的定义均相同。
R1可以代表以下基团:C1-C16 直链或支链饱和烷基,C2-C16 含双键、三键或芳环的直链或支链不饱和烷基,C3-C20
硅烷基,C1-C14 酰基;其中所述的每种基团中可以有0-3个氟,氯,溴,碘,氧,硫原子。
R2可以代表以下基团:C1-C16 直链或支链烷氧羰基,C2-C16
直链或支链烯烃氧羰基,C6-C16 直链或支链芳烃氧羰基,C1-C14 酰基,C1-C14 磺酰基;其中所述的每种基团中可以有0-3个氟,氯,溴,碘原子。
R3可以代表以下基团:氢,C1-C16 直链或支链饱和烷基,C2-C16 含双键、三键或芳环的直链或支链不饱和烷基,C3-C20
硅烷基,C1-C14 酰基,C1-C14 磺酰基;其中所述的每种基团中可以有0-3个氟,氯,溴,碘,氧,硫原子。
R4可以代表以下基团:氢,C1-C16 直链或支链饱和烷基,C2-C16 含双键、三键或芳环的直链或支链不饱和烷基;其中所述的每种基团中可以有0-3个氟,氯,溴,碘,氧,硫原子。
通式(
I
)化合物的制备:
通式(I)化合物是在有或没有催化剂(质子酸、路易斯酸等)和吸水剂(分子筛、硫酸钠等)的情况下,由化合物A与化合物B发生Pictet-Spengler环化反应得到的。化合物A中R1保护基优选苄基,R2保护基优选叔丁氧羰基(Boc),R3保护基优选烯丙基, 化合物B中R4保护基优选甲基。环化条件优选二氯甲烷和三氟乙醇为混合溶剂,乙酸为催化剂,4Å分子筛为吸水剂,反应温度为-60~120℃,反应时间为0.5~24h。
化合物A由已知的L-3-羟基-4-甲氧基-5-甲基-苯丙氨醇经四步得到的,当化合物A中R1保护基为苄基,R2保护基为Boc,R3保护基为烯丙基时,可按文献[J. Nat. Prod. 2013, 76, 1789]制备;R1,R2和R3为其它基团时,均按相似的策略获得。化合物B可方便地按照文献[Tetrahedron: Asymmetry 2010, 21, 39;
J. Heterocyclic Chem. 2010, 47, 50; Synlett 2009,
466; Tetrahedron Lett. 2003, 44, 4635.]中报道的多种方法制备。
发明效果
本发明提供了一类具有通式(I)的双四氢异喹啉化合物及其高效制备方法。通过化合物A和化合物B间的环化反应一步得到通式(I)化合物,而化合物A和B均可由已知文献及类似方法从L-酪氨酸高产率获得。从通式(I)化合物出发,经过已知五环化合物4,仅六步转化即可得到(-)-renieramycin
G,而且化合物4按文献还原C21位酰胺后可用于(-)-jorumycin等更多renieramycin型生物碱的合成。以通式(I)化合物为关键中间体来合成renieramycins生物碱及其类似物,使整个合成具有产率理想(例如以通式(I)中代表性的化合物D为中间体,从L-酪氨酸合成(-)-renieramycin
G总收率可达到15.8%)、灵活多用(可方便地合成C21位分别为酰胺和a-氨基腈/醇两种结构类型的生物碱)、原料试剂便宜、条件温和、操作简便、易于实现工业化等优点。与以前报道的renieramycins生物碱合成相比,有效地降低了成本和提高了效率,具有很好的应用前景。
下面列举实施例对本发明进行更为详细的说明,但本发明并不仅限于这些实施例。
1. 通式( I )代表化合物 D 的合成:
实施例
1
:化合物
A1
的制备:
往 250mL圆底烧瓶中加入100mL
CH2Cl2,21.6mmol草酰氯,在-78 °C下加入43.2mmol DMSO,搅拌20分钟,加入10.8mmol已知化合物C和10mL CH2Cl2的混合液。-78 °C下反应1h后,加入86.4mmol三乙胺。升温至0 °C,加入100mL水,分液后水相用乙酸乙酯萃取三次。有机液用饱和食盐水洗涤,无水Na2SO4干燥,浓缩后得到化合物A1粗品,可以不经纯化直接用于下一步反应。
实施例
2
:通式(
I
)代表化合物
D
的制备:
将上步的10.8mmol化合物A1粗品溶于90mL CH2Cl2和13mL三氟乙醇混合液,加入12.0mmol化合物B1,3.6mmol AcOH,5.0g 4Å分子筛。室温反应12h后,加入3.6mmol NaHCO3,搅拌后过滤。滤液浓缩后经色谱柱分离得化合物D,两步产率为62%;[α] D 20 = +2.0 (c = 1.2, in CH2Cl2);
IR (neat) ν max 3247, 2930,
2862, 1742, 1646, 1580, 1452, 1405, 1253, 1168, 1072,1001, 737 cm– 1; 1H NMR (400 MHz,
CDCl3): δ (ppm) 8.99 (br
s, 1H), 7.24–7.42 (m, 5H), 6.62 (s, 1H), 6.48 (s,
1H), 6.08 (m, 1H), 5.87 (dd, J = 10.8, 4.6 Hz, 1H), 5.43 (dd, J =
17.2, 1.2 Hz, 1H), 5.23 (dd, J = 10.4, 0.8 Hz, 1H), 5.15 (d, J =
5.6 Hz, 1H), 4.75 (d, J = 12.4 Hz, 1H), 4.71 (d, J = 12.5 Hz,
1H), 4.59 (dd, J = 12.7, 5.3 Hz, 1H), 4.48 (dd, J = 12.7, 5.2 Hz,
1H), 4.26 (dd, J = 11.1, 7.1 Hz, 1H), 4.00 (t, J = 10.8, 4.6 Hz,
1H), 3.83 (s, 3H), 3.77 (s, 3H), 3.70 (s, 3H), 3.68 (m, 1H), 3.46 (dd, J
= 10.5, 4.8 Hz, 1H), 2.88 (br d, J = 13.0 Hz, 1H), 2.81 (m, 1H),
2.68 (d, J = 5.2 Hz, 1H), 2.26 (s, 3H), 2.22 (m, 1H), 2.17 (s, 3H), 1.49
(s, 9H); 13C NMR (100 MHz, CDCl3) δ 173.5, 157.4, 149.2, 147.7, 147.5, 145.1, 139.3,
134.3, 131.8, 131.5, 130.8, 130.1, 128.3, 127.3, 126.9, 126.8, 125.5, 121.0,
119.4, 116.9, 81.3, 73.7, 71.6, 71.3, 60.2, 60.1, 68.4, 55.2, 53.0, 51.9, 49.9,
33.6, 28.5, 25.0, 15.9, 15.8; MS (ESI+): m/z [M+Na]+
725.3.
2.
通式(
I
)的代表化合物
D
到
(-)-renieramycin
G
的转化:
实施例
3
:化合物
E
的制备:
往 100mL圆底烧瓶中加入1.54mmol
化合物D,15mL 乙腈,加入1.20mL 37%甲醛水溶液,
3.08mmol NaBH3CN,3.08mmol AcOH。反应1h后,加入100mL CH2Cl2和30mL饱和NaHCO3,分液。水相用乙酸乙酯萃取两次。合并的有机液用饱和食盐水洗涤,无水Na2SO4干燥。浓缩后经色谱柱分离得化合物E,产率为92%;
[α]D 25 = +30 (c
= 1.2, in CHCl3); IR (neat) νmax:
3251, 2928, 2860, 1744, 1646, 1586, 1456, 1398, 1366, 1322, 1248, 1170, 1103,
1075, 1003, 923, 755 cm-1; 1H NMR (400 MHz, CDCl3):
δ (ppm) 9.18 (s, 1H), 7.20-7.38 (m, 5H),
6.63 (s, 1H), 6.47 (s, 1H), 6.1 (m, 1H), 5.94 (dd, J = 9.2, 4.0 Hz, 1H),
5.45 (d, J = 17.2 Hz, 1H), 5.24 (d, J = 10.4 Hz, 1H), 4.74 (s,
1H), 4.67 (d, J = 12.1 Hz, 1H), 4.62 (dd, J = 12.7, 5.4 Hz, 1H),
4.57 (d, J = 12.1 Hz, 1H), 4.49 (dd, J = 12.7, 5.4 Hz, 1H), 4.27
(t, J = 9.8 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 3H), 3.76 (m, 1H), 3.74 (s,
3H), 3.59 (dd, J = 10.2, 4.1 Hz, 1H), 3.26 (dd, J = 12.3, 3.6 Hz,
1H), 2.88 (m, 1H), 2.77 (dd, J = 15.0, 3.6 Hz, 1H), 2.59 (s, 3H), 2.26
(s, 3H), 2.24 (m, 1H), 2.18 (s, 3H), 1.47 (s, 9H); 13C NMR (100 MHz,
CDCl3): δ (ppm) 174.7,
157.8, 149.4, 147.5, 147.3, 145.4, 139.2, 134.4, 131.5, 131.4, 130.5, 128.7,
128.2, 127.6, 127.2, 126.9, 125.2, 120.3, 119.9, 117.0, 81.5, 73.7, 72.8, 71.9,
65.8, 61.4, 60.21, 60.17, 60.0, 52.0, 51.1, 47.3, 33.2, 28.4, 27.0, 15.9, 15.8;
MS (ESI+): m/z [M+H]+ 717.4.
实施例
4
:化合物
F
的制备:
往 50mL圆底烧瓶中加入0.88mmol化合物E,8mL MeOH,0.6mL浓盐酸。加热至50 °C,反应4h后,浓缩后加入50mL CH2Cl2和30mL水,加固体碳酸氢钠调至碱性,水相用CH2Cl2萃取两次。有机液用饱和食盐水洗涤,无水Na2SO4干燥。浓缩后经色谱柱分离得化合物F,产率为93%;[α]D 25
= -155 (c = 0.86, in CHCl3); IR (neat) νmax: 3280, 2931, 2862, 1635, 1580, 1491,
1448, 1318, 1233, 1102, 1076, 998, 753 cm-1; 1H NMR (400
MHz, CDCl3): δ (ppm) 7.09-7.20
(m, 3H), 6.85 (m, 2H), 6.73 (s, 1H), 6.50 (s, 1H), 6.26 (br s, 1H), 6.04
(m, 1H), 5.74 (m, 1H), 5.32 (dd, J = 17.2, 1.5 Hz, 1H), 5.17 (dd, J
= 10.4, 1.2 Hz, 1H), 4.51 (m, 2H), 4.28 (d, J = 3.2 Hz, 1H), 4.02 (dt, J
= 12.6, 2.6 Hz, 1H), 3.97 (m, 2H), 3.76 (s, 3H), 3.67 (d, J = 6.7 Hz,
1H), 3.63 (s, 3H), 3.59 (d, J = 4.3 Hz, 1H), 3.47 (dd, J = 10.4,
3.0 Hz, 1H), 3.21 (dd, J = 17.5, 6.8 Hz, 1H), 2.99 (dd, J = 14.8,
2.2 Hz, 1H), 2.89 (d, J = 17.4 Hz, 1H), 2.63 (t, J = 13.5 Hz,
1H), 22.45 (s, 3H), 2.23 (s, 3H), 2.19 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ (ppm) 171.1,
146.6, 145.9, 144.6, 143.4, 138.5, 133.1, 129.6, 129.5, 129.4, 128.1, 127.1,
126.9, 121.9, 120.9, 119.7, 116.5, 73.1, 72.1, 60.6, 60.5, 60.0, 58.3, 55.3,
50.0, 40.2, 32.3, 28.7, 15.80, 15.76; MS (ESI+): m/z [M+H]+ 585.3.
实施例
5
:化合物
G
的制备:
往 50mL圆底烧瓶中加入0.51mmol
化合物F,5.2mL
CH2Cl2,8.16mmol AcOH,0.10mmol Pd(Ph3P)4,3.06mmol n Bu3SnH。反应1.5h后,加入30 mL 10% NaHCO3水溶液和50mL CH2Cl2,分液。水相用CH2Cl2萃取两次。合并的有机液用无水Na2SO4干燥。浓缩后经色谱柱分离得化合物G,产率为98%;
[α]D 25 = -176 (c
= 1.1, in MeOH); IR (neat) νmax:
3388, 2929, 2860, 1767, 1717, 1637, 1497, 1452, 1378, 1312, 1235, 1187, 1077,
995, 736 cm-1; 1H NMR (400 MHz, CDCl3): δ (ppm) 7.10-7.20 (m, 3H), 6.89-6.94 (m, 2H), 6.52 (s,
1H), 6.49 (s, 1H), 6.49 (br s, 1H), 6.24 (br s, 1H), 5.73 (m,
1H), 4.26 (br s, 1H), 4.12 (d, J = 12.2 Hz, 1H), 4.05 (d, J
= 12.7 Hz, 1H), 4.02 (m, 1H), 3.73 (s, 3H), 3.67 (m, 2H), 3.65 (s, 3H), 3.44
(m, 1H), 3.21 (dd, J = 17.6, 6.7 Hz, 1H), 2.98 (d, J = 14.8 Hz,
1H), 2.87 (d, J = 17.5 Hz, 1H), 2.51 (t, J = 13.6 Hz, 1H), 2.44
(s, 3H), 2.24 (s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ (ppm) 171.1, 146.6, 145.9, 144.6,
143.4, 138.5, 133.1, 129.6, 129.5, 129.4, 128.1, 127.1, 126.9, 121.9, 120.9,
119.7, 116.5, 73.1, 72.1, 60.6, 60.5, 60.0, 58.3, 55.3, 50.0, 40.2, 32.3, 28.7,
15.8, 15.8; MS (ESI+): m/z [M+H]+
545.2.
实施例
6
:化合物
4
的制备:
往 50mL圆底烧瓶中加入0.46mmol
化合物G,5.0mL
MeOH,0.25mL HCO2H,0.25g 10% Pd/C。反应12h后,过滤后浓缩,加入5% NaHCO3水溶液和AcOEt,分液。有机相用无水Na2SO4干燥。浓缩后经色谱柱分离得化合物4,产率为94%;
[α]D 25 = -121 (c
= 0.80, in MeOH); IR (neat) νmax:
3331, 2931, 2849, 1618, 1496, 1449, 1419, 1313, 1235, 1095, 1067, 1004, 734 cm-1;
1H NMR (400 MHz, DMSO-d6): δ
(ppm) 8.86 (s, 1H), 8.70 (s, 1H), 6.45(s, 1H), 6.43 (s, 1H), 5.46 (m, 1H), 4.27
(br s, 1H), 4.17 (s, 1H), 3.81 (d, J = 11.1 Hz, 1H), 3.61 (s,
6H), 3.48 (d, J = 6.3 Hz,1H), 3.21 (m, 1H), 3.08 (dd, J = 17.4,
6.5 Hz, 1H), 2.99 (m, 1H), 2.90 (d, J = 14.8 Hz, 1H), 2.59 (d, J
= 17.3 Hz, 1H), 2.30 (m, 1H), 2.29 (s, 3H), 2.17 (s, 6H); 13C NMR
(100 MHz, DMSO-d6): δ (ppm) 170.5,
147.2, 146.5, 144.5, 143.7, 132.9, 129.2, 128.9, 128.8, 120.6, 119.9, 119.7,
117.3, 63.5, 59.81, 59.76, 59.2, 58.2, 54.6, 50.5, 39.6, 31.8, 28.0, 15.54,
15.5; MS (ESI+): m/z [M+H]+
455.2.
实施例
7
:化合物
H
的制备:
往 25mL圆底烧瓶中加入0.062mmol
化合物4,1.23mmol
当归酰氯,2.0mL CH2Cl2。室温反应4h,加入30mL CH2Cl2,用5% NaHCO3洗涤。有机相用无水Na2SO4干燥,浓缩后经色谱柱分离得化合物H,产率为93%;
[α]D 25 = -130 (c
= 1.2, in CH2Cl2); IR (neat) νmax: 3361, 2926, 2855, 1715, 1642, 1498,
1453, 1420, 1358, 1312, 1234, 1150, 1057, 997 cm-1; 1H
NMR (400 MHz, CDCl3): δ
(ppm) 6.47 (s, 2H), 6.19 (s, 1H), 6.06 (s, 1H), 5.81 (t, J = 3.6 Hz,
1H), 5.73 (qq, J = 7.2, 1.2 Hz, 1H), 2.29 (m, 2H), 4.24 (d, J =
3.2 Hz, 1H), 3.98 (m, 1H), 3.76 (s, 3H), 3.73 (s, 3H), 3.66 (d, J = 7.0
Hz, 1H), 3.16 (dd, J = 17.6, 7.0 Hz, 1H), 2.97 (dd, J = 15.1, 2.1
Hz, 1H), 2.85 (d, J = 17.6 Hz, 1H), 2.46 (m, 1H), 2.42 (s, 3H), 2.22 (s,
3H), 2.22 (s, 3H), 1.63 (dq, J = 7.2, 1.4 Hz, 3H), 1.36 (t, J =
1.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 171.4, 167.2, 146.5, 145.8, 144.0, 143.2, 137.4,
133.6, 129.7, 129.6, 129.3, 127.7, 122.2, 120.7, 117.8, 116.3, 64.3, 60.73,
60.72, 60.0, 58.5, 55.2, 49.3, 40.3, 32.2, 28.5, 20.1, 15.84, 15.80, 15.4; MS
(ESI+): m/z [M+Na]+ 559.2.
实施例
8
:
(-)-renieramycin
G
的制备:
往 25mL圆底烧瓶中加入0.041mmol
化合物H,2.0mL
乙腈,0.021mmol salcomine。氧气氛围下反应5h后过滤,乙酸乙酯洗涤滤渣。滤液浓缩后经色谱柱分离得到(-)-renieramycin
G,产率为92%; [α]D 26
= -160 (c = 0.5, in CH2Cl2); IR (neat) νmax: 2925, 2854, 1716, 1656, 1615, 1452,
1423, 1307, 1230, 1149, 1046 cm-1; 1H NMR (400 MHz, CDCl3):
δ (ppm) 5.89 (m, 1H), 5.38 (br s,
1H), 4.66 (dd, J = 11.7, 2.6 Hz, 1H), 4.31 (dd, J = 11.6, 2.4 Hz,
1H), 4.12 (d, J = 3.4 Hz, 1H), 4.00 (s, 3H), 3.96 (s, 3H), 3.85 (br
d, J = 12.4 Hz, 1H), 3.67 (d, J = 6.6 Hz, 1H), 3.00 (dd, J
= 16.5, 2.5 Hz, 1H), 2.86 (dd, J = 20.8, 6.8 Hz, 1H), 2.64 (d, J
= 20.8 Hz, 1H), 2.36 (s, 3H), 1.91 (s, 6H), 1.67 (dq, J = 7.3, 1.5 Hz,
3H), 1.51 (t, J = 1.4 Hz, 1H), 1.47 (ddd, J = 16.6, 12.4, 1.6 Hz,
1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 186.6, 185.6, 182.8, 180.8, 170.6, 167.3, 156.5,
155.9, 142.5, 142.0, 139.8, 136.5, 135.3, 129.7, 128.8, 127.1, 63.2, 61.4,
61.3, 59.4, 56.5, 53.3, 50.5, 40.1, 26.0, 23.9, 20.6, 15.7, 8.9, 8.8; MS (ESI+):
m/z [M+Na]+ 587.2.
Claims (2)
1.如通式(I)所示的化合物:
通式(I)中R1可以代表以下基团:C1-C16
直链或支链饱和烷基,C2-C16
含双键、三键或芳环的直链或支链不饱和烷基,C3-C20 硅烷基,C1-C14 酰基;其中所述的每种基团中可以有0-3个氟,氯,溴,碘,氧,硫原子;
R2可以代表以下基团:C1-C16 直链或支链烷氧羰基,C2-C16 直链或支链烯烃氧羰基,C6-C16 直链或支链芳烃氧羰基,C1-C14 酰基,C1-C14 磺酰基;其中所述的每种基团中可以有0-3个氟,氯,溴,碘原子;
R3可以代表以下基团:氢,C1-C16 直链或支链饱和烷基,C2-C16 含双键、三键或芳环的直链或支链不饱和烷基,C3-C20 硅烷基,C1-C14 酰基,C1-C14 磺酰基;其中所述的每种基团中可以有0-3个氟,氯,溴,碘,氧,硫原子;
R4可以代表以下基团:氢,C1-C16 直链或支链饱和烷基,C2-C16 含双键、三键或芳环的直链或支链不饱和烷基;其中所述的每种基团中可以有0-3个氟,氯,溴,碘,氧,硫原子。
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