CN107344957A - A kind of cyclic ester peptide. and its preparation method and application - Google Patents
A kind of cyclic ester peptide. and its preparation method and application Download PDFInfo
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Abstract
The invention belongs to medicinal chemistry arts.It is related to cyclic ester peptide. Oxoapratoxin E of a kind of formula (I) structure and its preparation method and application.The cyclic ester peptide. first synthesizes cyclization precursors when preparing, close big ring after removing N ends and C ends protection group and then cyclic ester peptide. of the invention is formed using dehydrated reagent.The cyclic ester peptide. of the present invention is through anti tumor activity in vitro screening experiment, the results showed that, there is stronger antitumor activity, there is potential application value in terms of the research and development of field of medicaments especially antineoplastic.
Description
Technical field
The invention belongs to medicinal chemistry arts.It is related to a kind of cyclic ester peptide. and its preparation method and application.
Background technology
Prior art discloses Apratoxin be discovered in recent years the most strong marine natural products of antitumor activity it
One, its half-inhibition concentration to tumour cell nanomole and picomole rank ((a) is big etc., organic chemistry, 2014,34,
475；(b) Tarsis, E.M.et al.Tetrahedron 2015,71,5029；(c)Doi,
T.Chem.Pharm.Bull.2014,62,735；(d) Luesch, H.et al.J.Am.Chem.Soc.2001,123,5418).
One of member in the studies have shown that family, apratoxin E (Matthew, S.et al.J.Nat.Prod.2008,71,
1113) there is extremely strong lethal effect to cancer cells such as colon cancer, cervical carcinoma and osteocarcinoma, be expected to exploitation makes for antineoplastic
With.However, the natural products contains thiazoline ring that is unstable and being difficult chemical preparation, which has limited its application.
Present situation based on prior art, present inventor intend providing cyclic ester peptide. and its preparation side of a kind of new structure
Method and application.
The content of the invention
The purpose of the present invention is the defects of overcoming prior art, there is provided a kind of cyclic ester peptide. of new structure and its preparation side
Method.
The further object of the present invention is to provide purposes of the described cyclic ester peptide. in pharmacy.
The invention provides the cyclic ester peptide. of the chemical constitution as shown in following formula (I), its molecular formula is C43H65N5O8,
Thiazoline ring in apratoxin E is replaced with to oxazoline ring (such as following formula (II) being relatively easily-synthesized in the present invention
It is shown), cyclization precursors are first synthesized during preparation, big ring is closed after removing N- ends and C- ends protection group and then uses dehydrated reagent,
Be made new cyclic ester peptide. structure, the new cyclic ester peptide. there is good antitumor activity and overcome natural products be not easy to obtain and
The defects of less stable.
Specifically, the cyclic ester peptide. of the present invention is prepared by following methods, it includes step：Using following formula compound I and
II, compound III is formed under condensing agent effect；R is C1~C10 straight or branched alkyl, aromatic radical, pi-allyl in formula；
The condensing agent used is 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, 2- (7- azos BTA)-N,
N, N', N'- tetramethylurea hexafluorophosphoric acid ester, (3H-1,2,3- triazols [4,5-b] pyridine -3- epoxides) three -1- Bi cough up Wan Ji Phosphonium
Hexafluorophosphate, 3- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone or its combination；Solvent for use is dichloromethane
Alkane, tetrahydrofuran, N,N-dimethylformamide or its combination；Reaction temperature is -10~80 degrees Celsius；Reaction time be 0.5~
30 hours；
After compound III is handled with trifluoroacetic acid cyclization precursors compound is formed with compound IV under condensing agent effect
V；The condensing agent used be 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, 2- (7- azos BTA) -
N, N, N', N'- tetramethylurea hexafluorophosphoric acid ester, (3H-1,2,3- triazols [4,5-b] pyridine -3- epoxides) three -1- pyrrolidinyls
Phosphonium hexafluorophosphate, 3- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone or its combination；Solvent for use is dichloro
Methane, tetrahydrofuran, N,N-dimethylformamide or its combination；Reaction temperature is -10~80 degrees Celsius；Reaction time is 0.5
~30 hours；In compound V, R is C1~C10 straight or branched alkyl, aromatic radical, pi-allyl, and R1 is tertbutyloxycarbonyl, 9-
Fluorenylmethoxycarbonyl, benzyloxycarbonyl group, 2,2,2- tri-chloroethoxy base carbonyls；
R in compound V and R1 are converted into hydrogen, in of the invention, according to R and R1 difference, the condition used is hydrogen
The solution of the inorganic bases such as sodium oxide molybdena, catalytic hydrogenation, acid cleavage etc., then form compound VI under condensing agent effect；Use
Condensing agent is 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, 2- (7- azos BTA)-N, N, N',
N'- tetramethylurea hexafluorophosphoric acids ester, (3H-1,2,3- triazols [4,5-b] pyridine -3- epoxides) three -1- Bi cough up Wan Ji Phosphonium hexafluoros
Phosphate, 3- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone or its combination；Solvent for use is dichloromethane, four
Hydrogen furans, N,N-dimethylformamide or its combination；Reaction temperature is -10~80 degrees Celsius；Reaction time is 0.5~30 small
When；
Compound VI is handled to obtain to the cyclic ester peptide. of described formula (I) structure with dehydrated reagent；Wherein, used dehydration
Reagent is diethylin sulfur trifluoride, methoxyl group carbonyl disulon acyl) triethylammonium hydroxide；Solvent for use is dichloromethane, four
Hydrogen furans, N,N-dimethylformamide or its combination；Reaction temperature is -80~50 degrees Celsius；Reaction time is 0.5~30 small
When.
Cyclic ester peptide. Oxoapratoxin E produced by the present invention have carried out anti tumor activity in vitro screening experiment, as a result table
Bright, cyclic ester peptide. Oxoapratoxin E of the invention have stronger antitumor activity, can be further used for preparing antineoplastic.
The commercial reagents that the cyclic ester peptide. of the present invention can be readily synthesized or be bought by some carry out artificial synthesized preparation.
Embodiment
Embodiment 1 prepares cyclic ester peptide., specifically includes following steps：
1st, prepare linear tetrapeptide (by taking R=pi-allyls as an example)
Take compound I (by literature method prepare, referring to：Doi,T.；Numajiri,Y.；Munakata,A.；
Takahashi, T.Org.Lett.2006,8,531-534.) 492mg (1.1mmol) is dissolved in 10mL dry methylene chlorides, adds
Enter compound II (301.2mg, 1.1mmol) and HATU (627.4mg, 1.65mmol), ice bath be added dropwise DIPEA (576.0 μ L,
3.3mmol).12h is stirred at room temperature under nitrogen protection, LC-MS display reactions are complete.Saturated ammonium chloride is quenched, dchloromethane,
The washing of 5% aqueous potassium hydrogen sulfate is closely colourless to aqueous phase for several times, saturated sodium-chloride washing, anhydrous sodium sulfate drying, is concentrated under reduced pressure.
Crude product is through silica gel column chromatography (PE:EA=3:1) 570.3mg white solid III, yield 73.4% are obtained.[α]D 25=-109.4 (c
1.0,CHCl3)；Rf=0.29 (PE:EA=2:3)；1HNMR(400MHz,CDCl3):δ 7.13and 7.08 (both d, J=
8.0Hz, total 2H), 6.86and 6.78 (both d, J=8.4Hz, total 2H), 5.94-5.79 (m, 1H), 5.40
(dd, J=13.7,6.8Hz, 1H), 5.32-5.15 (m, 3H), 4.94 (d, J=10.4Hz, 1H), 4.60 (d, J=4.8Hz,
2H), 3.93-3.82 (m, 1H), 3.77 (s, 3H), 3.70-3.54 (m, 1H), 3.04 (dd, J=13.4,7.2Hz, 1H), 2.98
(s,3H),2.91–2.83(m,1H),2.78and 2.71(both s,total 3H),2.27–2.06(m,2H),1.96(m,
2H),1.83–1.76(m,1H),1.71(br,1H),1.59and 1.53(both s,total 3H),1.49and 1.45
(both s, total 12H), 1.31-1.24 (m, 4H), 1.02-0.97 (m, 1H), 0.94 (d, J=6.4Hz, 3H), 0.86
(t, J=6.9Hz, 3H)；13C NMR(100MHz,CDCl3)δ171.9,171.5,170.7,158.6,152.8,131.7,
130.5,128.4,119.9,118.7,113.8,93.5,80.4,67.3,67.0,66.0,65.4,60.5,56.5,55.2,
50.4,49.7,37.5,33.3,33.1,30.9,30.5,30.2,29.9,29.3,28.5,27.7,26.7,25.0,24.4,
23.1,16.1,15.8,14.3,11.6,10.6；HR MS(ESI–TOF)calcd for[C37H58N4O9+Na]+725.4096,
found 725.4112；
2nd, introduce prolyl aliphatic chain fragment, prepare cyclization precursors (by taking R=pi-allyls, R1=9- fluorenylmethoxycarbonyls as an example)
Compound III (570.0mg, 0.81mmol) is taken to be dissolved in 6mL dichloromethane, ice bath adds 6mL trifluoroacetic acids, ice
Bath stirring 1h.TCL and LC-MS display reactions are complete, are concentrated under reduced pressure, and once, vacuum drying 2h must take off Boc and propylidene to toluene azeotropic
The intermediate of protection group.This intermediate is dissolved in 10mL dry methylene chlorides, sequentially adds compound IV (by literature method system
It is standby, referring to：Chen,Q.-Y.；Liu,Y.；Cai,W.；Luesch,H.J.Med.Chem.2014,57,3011-3029)
DIPEA (425.0 μ L, 2.43mmol), room is added dropwise in 430.0mg (0.81mmol) and HATU (462.0mg, 1.22mmol), ice bath
Temperature stirring 18h.Saturated ammonium chloride is quenched, dchloromethane, and 5% aqueous potassium hydrogen sulfate washs, saturation closely colourless to aqueous phase
NaCl, anhydrous sodium sulfate drying, it is concentrated under reduced pressure.Crude product is through silica gel column chromatography (DCM:MeOH=20:1) 550.1mg is obtained
White solid V, yield 63.3%.[α]D 25=-81.7 (c 0.3, CHCl3)；1HNMR(400MHz,CDCl3) δ 7.76 (d, J=
7.1Hz, 2H), 7.65-7.57 (m, 2H), 7.40 (t, J=7.2Hz, 2H), 7.31 (t, J=7.3Hz, 2H), 7.14-7.04
(m, 2H), 6.91-6.74 (m, 4H), 5.94-5.73 (m, 2H), 5.40 (dd, J=13.7,6.8Hz, 1H), 5.32-5.27 (m,
1H), 5.25-5.22 (m, 1H), 5.21-5.14 (m, 1H), 4.93 (d, J=10.4Hz, 2H), 4.60 (d, J=4.5Hz, 2H),
4.50–4.24(m,3H),4.19–4.06(m,1H),3.75(s,3H),3.72–3.58(m,2H),3.56–3.30(m,2H),
3.03 (s, 1H), 2.99 (s, 3H), 2.85 (d, J=7.5Hz, 1H), 2.82-2.77 (m, 1H), 2.74 (d, J=3.2Hz,
2H),2.48–2.33(m,1H),2.27–2.19(m,1H),2.17–2.09(m,2H),2.02–1.85(m,3H),1.82–1.51
(m,6H),1.43–1.37(m,2H),1.30–1.25(m,4H),1.00–0.67(m,21H)；13C NMR(100MHz,CDCl3)δ
172.4,171.9,171.5,170.7,158.6,154.9,143.9,143.5,143.1,141.3,131.7,130.4,
127.8,127.7,127.1,125.5,125.2,120.0,118.7,113.9,79.5,79.1,67.8,67.5,65.4,
64.8,60.5,59.5,59.2,55.2,51.2,50.4,49.7,47.2,47.0,46.4,37.7,37.2,36.9,36.6,
34.8,34.6,33.3,32.4,31.2,31.0,30.5,30.0,26.9,26.5,26.0,25.0,24.2,23.2,21.0,
20.6,15.8,14.3,10.6；HR MS(ESI–TOF)calcd for[C61H83N5O12+H]+1078.6111,found
1078.6115；
3rd, remove protection group, close big ring (by taking R=pi-allyls, R1=9- fluorenylmethoxycarbonyls as an example)
Compound V (253mg) is dissolved in 10mL dry tetrahydrofurans, argon gas protection is lower to add tetrakis triphenylphosphine palladium
(27mg) and methylphenylamine (64 μ L), are stirred at room temperature 2h, are concentrated under reduced pressure, concentrate is diluted with ethyl acetate, 5% potassium acid sulfate
The aqueous solution washs, saturated sodium-chloride washing, anhydrous sodium sulfate drying.Crude product obtains white solid through silica gel column chromatography.By this solid
It is dissolved in 5mL acetonitriles, adds 5mL diethylamine, 1h is stirred at room temperature under argon gas protection, TLC display reactions are complete, are concentrated under reduced pressure,
Once, this crude product is dissolved in 30mL dry methylene chlorides by vacuum after draining 2h for dichloromethane and each azeotropic of toluene, adds
DIPEA (64.5 μ L, 0.37mmol) is added dropwise in HATU (51.7mg, 0.14mmol), ice bath.12h is stirred at room temperature under nitrogen protection,
LC-MS display reactions are complete.Saturated ammonium chloride is quenched, and 5% aqueous potassium hydrogen sulfate washs closely colourless to aqueous phase for several times, saturation chlorine
Change sodium washing, anhydrous sodium sulfate drying, be concentrated under reduced pressure.Crude product is through silica gel column chromatography (CHCl3:MeOH=10:1) it is white to obtain 49.5mg
Color solid VI, yield 55.4%.[α]D 25=-109.0 (c 0.3, CHCl3)；1HNMR(400MHz,CDCl3) δ 7.11 (d, J=
8.4Hz, 2H), 6.84 (d, J=8.5Hz, 2H), 6.45 (d, J=9.0Hz, 1H), 5.95 (d, J=15.5Hz, 1H), 5.31
(s, 3H), 4.92 (t, J=10.6Hz, 2H), 4.75 (d, J=6.0Hz, 1H), 4.36-4.31 (m, 1H), 4.10-4.02 (m,
1H),3.78(s,3H),3.67(s,3H),3.11–2.99(m,2H),2.95(s,3H),2.90–2.84(m,2H),2.78–
2.73(m,1H),2.66(s,3H),2.46–2.36(m,1H),2.30–2.20(m,1H),2.19–2.09(m,1H),2.05–
1.69 (m, 9H), 1.59-1.37 (m, 1H), 1.35-1.20 (m, 2H), 1.12 (dd, J=10.6,7.1Hz, 1H), 1.06 (d, J
=6.5Hz, 2H), 1.00-0.92 (m, 3H), 0.88-0.66 (m, 15H)；13C NMR(100MHz,CDCl3)δ172.5,
171.9,171.6,170.1,169.9,168.8,158.9,145.5,130.3,127.9,124.1,114.3,113.9,66.2,
59.4,58.0,55.4,54.7,53.7,53.5,50.1,47.4,40.0,37.3,36.7,35.2,34.0,32.6,30.5,
30.0,29.4,28.9,25.9,25.8,25.7,25.2,19.1,15.2,14.1,13.0,9.9；HR MS(ESI–TOF)
calcd for[C43H67N5O9+H]+798.5012,found 798.4998；
4th, it is dehydrated, prepares target product cyclic ester peptide. Oxoapratoxin E
Compound VI (40.0mg, 0.05mmol) is dissolved in 2mL dry methylene chlorides, -78 DEG C add DAST (56.0 μ L,
0.46mmol), after stirring 30min, pyridine (56.0 μ L) is added, 30min is stirred at room temperature.LC-MS display reactions are complete.Saturation chlorine
Change ammonium to be quenched, dchloromethane, saturated sodium-chloride washing, anhydrous sodium sulfate drying, be concentrated under reduced pressure.Crude product prepares thin layer, obtains
17.6mg white solid Oxoapratoxin E, yield 44.5%.[α]D 25=-30.5 (c 0.12, MeOH)；1HNMR
(600MHz,CDCl3) δ 7.13 (d, J=7.9Hz, 2H, C21/25), 6.81 (d, J=7.5Hz, 2H, C22/24),6.63and 6.52
(both m,total 1H,C35), 6.32 (d, J=15.8Hz, 1H, C34), 6.03and 5.95 (both d, J=8.8and
15.1Hz, total1H, NH), 5.24and 4.98 (both d, J=11.4Hz, total 1H, C7),5.18and 4.87
(both d, J=11.0and 10.7Hz, total 1H, C18), 4.91 (dd, J=11.3,6.1Hz, 1H, C39),4.67and
4.22 (both dd, J=12.9,6.4and 15.8,7.5Hz, total 1H, C2), 4.28and 3.31 (both q, J=
8.8and 6.4Hz,total 1H,C14),4.10and 4.01(both m,total 1H,C5a),3.85(m,1H),
3.774and 3.768(both s,total 3H,C26),3.65(m,1H,C5b),3.08(m,1H,C19a), 2.93 (dd, J=
12.6,3.6Hz,1H,C19b),3.03and 2.86and 2.82(all s,total 3H,C12),2.80and
2.74and2.63(all s,total 3H,C16),2.60(m,1H,C28),2.40(m,1H),2.26(m,1H,C3a),
2.22and1.03 (both t, J=7.44and 6.36Hz, total 3H, C10),2.04(m,4H),2.01and 0.55
(both d, J=5.7and 6.4Hz, total 3H, C11),1.99(m,1H),1.93(m,2H),1.85(m,1H,C3a),
1.71 (m, 2H), 1.65-1.59 (m, 2H), 1.42 (m, 1H), 1.25 (m, 2H), 1.07and 0.55 (both d, J=
6.4and 6.3Hz,total 3H,C11),0.92(m,3H,C45),0.89and 0.88and 0.87(all s,total9H,
C41/42/43)；13C NMR(100MHz,CDCl3)δ172.0,171.7,171.2,171.1,170.8,168.9,158.6,151.7,
151.6,146.6,141.0,134.9,130.4,129.9,129.5,129.4128.0,127.0,126.7,125.6,121.0,
120.7,119.7,119.1,114.1,113.9,80.5,80.2,71.9,66.8,65.1,60.8,59.5,59.2,58.0,
56.3,55.4,55.2,50.3,49.5,48.6,47.3,47.1,45.9,41.8,40.6,39.9,38.2,37.7,36.5,
36.4,36.0,35.2,34.9,34.8,34.1,33.0,32.9,31.9,31.4,30.5,30.0,29.8,29.6,29.3,
29.2,29.1,27.2,26.1,26.0,25.9,25.6,24.5,24.1,23.1,22.7,20.7,20.5,19.4,15.6,
14.8,14.5,14.2,13.0,11.7,10.6；HR MS(ESI–TOF)calcd for[C43H65N5O8+H]+780.4906,
found 780.4902。
The anti tumor activity in vitro screening experiment of embodiment 2
Cyclic ester peptide. Oxoapratoxin E anti tumor activity in vitro screening experiments have been carried out in the present embodiment, have been used
Staurosporine is positive control, uses tetrazolium reducing process and Sulforhodamine B protein stainings method as screening technique；
Using 4 kinds of tumor cell line A549, HCT 116, Hela, MCF-7 (tumor cell line is commercially available) has carried out active testing,
As a result show (as shown in table 1), cyclic ester peptide. Oxoapratoxin E of the invention have stronger antitumor activity, in field of medicaments
Especially there is potential application value in terms of the research and development of antineoplastic.
The compound Oxoapratoxin E antitumor activities (IC of table 150/μM)
Claims (9)
- The cyclic ester peptide. of formula 1. (I) structure, its molecular formula is C43H65N5O8,
- 2. the preparation method of the cyclic ester peptide. described in claim 1, it is characterized in that, it includes：Using the compound I and II being shown below, compound III is formed under condensing agent effect,Cyclization precursors compound V is formed under condensing agent effect with compound IV after compound III is handled with trifluoroacetic acid,R in compound V and R1 are converted into hydrogen, then form compound VI under condensing agent effect,Compound VI is handled with dehydrated reagent to obtain the cyclic ester peptide. of formula (I) structure.
- 3. the preparation method of cyclic ester peptide. as claimed in claim 2, it is characterized in that, described compound I and II makees in condensing agent In being reacted with lower formation compound III, straight or branched alkyls of the R selected from C1~C10, aromatic radical, pi-allyl in formula；Use Condensing agent is selected from 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, 2- (7- azos BTA)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid ester, (3H-1,2,3- triazols [4,5-b] pyridine -3- epoxides) three -1- Bi cough up Wan Ji Phosphonium six Fluorophosphate, 3- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone or its combination；Solvent for use is selected from dichloromethane Alkane, tetrahydrofuran, N,N-dimethylformamide or its combination；Reaction temperature is -10~80 degrees Celsius；Reaction time be 0.5~ 30 hours.
- 4. the preparation method of cyclic ester peptide. as claimed in claim 2, it is characterized in that, after compound III is handled with trifluoroacetic acid Formed with compound IV under condensing agent effect in cyclization precursors compound V reactions, the condensing agent used is selected from 1- (3- diformazan ammonia Base propyl group) -3- ethyl-carbodiimide hydrochlorides, 2- (7- azos BTA)-N, N, N', N'- tetramethylurea hexafluorophosphoric acids Ester, (3H-1,2,3- triazols [4,5-b] pyridine -3- epoxides) three -1- Bi cough up Wan Ji Phosphonium hexafluorophosphate, 3- (diethoxy phosphorus Acyloxy) -1,2,3- phentriazine -4- ketone or its combination；Solvent for use is dichloromethane, tetrahydrofuran, N, N- dimethyl methyls Acid amides or its combination；Reaction temperature is -10~80 degrees Celsius；Reaction time is 0.5~30 hour.
- 5. the preparation method of cyclic ester peptide. as claimed in claim 2, it is characterized in that, in the compound V, R is the straight of C1~C10 Chain or branched alkyl, aromatic radical, pi-allyl；R1 is tertbutyloxycarbonyl, 9- fluorenylmethoxycarbonyls, benzyloxycarbonyl group or 2,2,2- tri-chloroethoxies Base carbonyl.
- 6. the preparation method of cyclic ester peptide. as claimed in claim 2, it is characterized in that, the R in compound V and R1 are converted into hydrogen When, according to R and R1 difference, the condition used is the solution of inorganic base, catalytic hydrogenation or acid cleavage.
- 7. the preparation method of cyclic ester peptide. as claimed in claim 2, it is characterized in that, the R in compound V and R1 are converted into hydrogen, Then formed under condensing agent effect in compound VI reactions, the condensing agent used is 1- (3- dimethylamino-propyls) -3- ethyls Carbodiimide hydrochloride, 2- (7- azos BTA)-N, N, N', N'- tetramethylurea hexafluorophosphoric acids ester, (3H-1,2,3- tri- Azoles simultaneously [4,5-b] pyridine -3- epoxides) three -1- Bi cough up Wan Ji Phosphonium hexafluorophosphate, 3- (diethoxy phosphoryl oxy) -1,2,3- Phentriazine -4- ketone or its combination；Solvent for use is dichloromethane, tetrahydrofuran, N,N-dimethylformamide or its combination；Instead It is -10~80 degrees Celsius to answer temperature；Reaction time is 0.5~30 hour.
- 8. the preparation method of cyclic ester peptide. as claimed in claim 2, it is characterized in that, compound VI is handled to obtain with dehydrated reagent Described cyclic ester peptide., wherein, dehydrated reagent is diethylin sulfur trifluoride, methoxyl group carbonyl disulon acyl) triethylammonium hydroxide； Solvent for use is dichloromethane, tetrahydrofuran, N,N-dimethylformamide or its combination；Reaction temperature is -80~50 degrees Celsius； Reaction time is 0.5~30 hour.
- 9. application of the cyclic ester peptide. described in claim 1 in antineoplastic is prepared.
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| CN114085272A (en) * | 2022-01-10 | 2022-02-25 | 中山大学 | Isaridin cyclic depsipeptide derivative and preparation method and application thereof |
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| DOI, T.等: "Total Synthesis of Apratoxin A", 《ORGANIC LETTERS》 * |
| GILLES, A.等: "Supported Synthesis of Oxoapratoxin A", 《J. ORG. CHEM.》 * |
| YOSHIDA, M.等: "Potent oxazoline analog of apratoxin C: Synthesis, biological evaluation, and conformational analysis", 《PEPTIDESCIENCE》 * |
| 张伟等: "海洋抗肿瘤环酯肽Apratoxin A 研究进展", 《有机化学》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114085272A (en) * | 2022-01-10 | 2022-02-25 | 中山大学 | Isaridin cyclic depsipeptide derivative and preparation method and application thereof |
| WO2023130740A1 (en) * | 2022-01-10 | 2023-07-13 | 中山大学 | Isaridin cyclic lipopeptide derivative, and preparation method therefor and use thereof |
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