Synthesis and Cytotoxic Activities of α‐Methylidene‐γ‐butyrolactones Bearing a Quinolin‐4(1H)‐one Moiety

The cytotoxicities of the α‐methylidene‐γ‐butyrolactones 4 , 5 , and 8 , which are linked to a quinolin‐4(1H)‐one moiety through a piperazine or O‐atom bridge were studied. These compounds were synthesized by alkylation of 1‐ethyl‐6‐fluoro‐1,4‐dihydro‐7‐hydroxy‐4‐oxoquinoline‐3‐carboxylic acid ( 6 ) followed by a Reformatsky‐type condensation. Compounds 4 , 5 , and 8 were evaluated in vitro against 60 human‐tumor cell lines derived from nine cancer‐cell types and demonstrated not only strong growth‐inhibitory activities against leukemia cancer cells, but also fairly good activities against the growth of certain solid tumors (see Table). The O‐bridged derivatives 8a and 8b exhibit both cytostatic (mean log GI₅₀=−5.20 and −5.82, resp.) and cytocidal (mean log LC₅₀=−4.30 and −4.93, resp.) effects, while the piperazine‐bridged analogues 4 and 5 possess only weak cytostatic (mean log GI₅₀=−5.19 and −4.74, resp.; mean log LC₅₀>−4.00) capability. Among them, 8b is the most potent, with log GI₅₀=−6.47, −6.72, −6.53, and −6.52 against leukemia, SW‐620 (colon), Lox IMV1, and SK‐MEL‐28 (melanoma) cancer cells, respectively.     

Geiparvarin Analogues: Synthesis and Anticancer Evaluation of α-Methylidene-γ-butyrolactone-Bearing Coumarins

To determine some of the structural features of geiparvarin that account for its cytostatic activity in vitro, certain geiparvarin analogues modified in the furan-3(2H)-one moiety and the alkenyloxy substituent were synthesized and tested against the growth of 60 human cancer cell lines derived from nine cancer-cell types. These compounds demonstrated a strong growth-inhibitory activity against leukemia cell lines but were relatively inactive against non-small-cell lung cancers and CNS cancers. Comparison of the mean log GI₅₀ values of γ-[(E)-1-methylprop-1-enyl]-α-methylidene-γ-butyrolactones 7 – 9 revealed that 7-[(E)-3-(2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl)but-2-enyloxy]-2H- 1-benzopyran-2-one ( 8 ; −5.47) was more active than its 6-substituted counterpart 7 (−5.21) and its 3-chloro-4-methyl derivative 9 (−5.31) and had a potency similar to that of geiparvarin (log GI₅₀=−5.41). These results indicated that the furan-3(2H)-one moiety of geiparvarin could be replaced by an α-methylidene-γ-butyrolactone unit without losing the anticancer potency, and that the best substitution site at the coumarin moiety was C(7). The alkenyloxy substituent of 8 was also replaced by a methoxy substituent. Among these α-methylidene-γ-butyrolactones, 7-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenylfuran-2-yl)methoxy]-2H-1-benzopyran-2-one ( 11 ) was the most potent with a mean log GI₅₀ value of −5.83 and a range value of 132 (10^2.12).     

Efficient Synthesis of α‐Benzylidene‐γ‐methyl‐γ‐butyrolactones

A concise synthesis of α‐benzylidene‐γ‐methyl‐γ‐butyrolactones 5a – g from substituted benzaldehydes is described. Compounds 1a – g on reaction with phosphorane 2 , provide the pentenoates 3a – g , which can be hydrolyzed to the acids 4a – g . The latter are cyclized to the corresponding butyrolactones 5a – g in excellent yields. The pentenoates 3a – g , on acid catalyzed cyclization, also provide 5a – g in very high yields.     

Synthesis and Evaluation of α-Methylidene-γ-butyrolactone bearing flavone and xanthone moieties

In a search for inhibitors of platelet aggregation, a number of α-methylidene-γ-butyrolactones 5 and 6 bearing flavone or xanthone moieties, respectively, were synthesized and evaluated for their antiplatelet activity against thrombin(Thr)-, arachidonic-acid(AA)-, collagen(Col)?, and platelet-activating-factor(PAF)-induced aggregation in washed rabbit platelets. These compounds were synthesized from 7-hydroxyflavone ( 1 ) or 3-hydroxyxanthone ( 2 ) via O-alkylation (→ 3 and 4 , resp.) and Reformatsky-type condensation (Scheme). Most of the flavone-containing α-methylidene-γ-butyrolactones 5a – d showed potent antiplatelet effects on AA- and Col-induced aggregation, while xanthone derivatives 6c – e were found to have the same pharmacological profile than aspirin in which only AA-induced aggregation was inhibited (Table 1). However, 6c – e were approximately three to ten times more potent than aspirin (Table 2). For the vasorelaxing effects, 5a was the only compound which exhibited significant inhibitory activity on the high-K⁺ medium, Ca²⁺-induced vasoconstriction (Table3). Both 5a and 6a , with an aliphatic Me substituent at C(γ) of the lactone, were active against norepinephrine-induced phasic and tonic constrictions while their γ-aryl-substituted counterparts 5b – f and 6b – f were inactive.     

Synthesis and Antiplatelet‐Activity Evaluation of α‐Methylidene‐γ‐butyrolactones Bearing 3,4‐Dihydroquinolin‐2(1H)‐one Moieties

In continuation of our search for potent antiplatelet agents, we have synthesized and evaluated several α‐methylidene‐γ‐butyrolactones bearing 3,4‐dihydroquinolin‐2(1H)‐one moieties. O‐Alkylation of 3,4‐dihydro‐8‐hydroxyquinolin‐2(1H)‐one ( 1 ) with chloroacetone under basic conditions afforded 3,4‐dihydro‐8‐(2‐oxopropoxy)quinolin‐2(1H)‐one ( 2a ) and tricyclic 2,3,6,7‐tetrahydro‐3‐hydroxy‐3‐methyl‐5H‐pyrido[1,2,3‐de][1,4]benzoxazin‐5‐one ( 3a ) in a ratio of 1 : 2.84. Their Reformatsky‐type condensation with ethyl 2‐(bromomethyl)prop‐2‐enoate furnished 3,4‐dihydro‐8‐[(2,3,4,5‐tetrahydro‐2‐methyl‐4‐methylidene‐5‐oxofuran‐2‐yl)methoxy]quinolin‐2(1H)‐one ( 4a ), which shows antiplatelet activity, in 70% yield. Its 2′‐Ph derivatives, and 6‐ and 7‐substituted analogs were also obtained from the corresponding 3,4‐dihydroquinolin‐2(1H)‐ones via alkylation and the Reformatsky‐type condensation. Of these compounds, 3,4‐dihydro‐7‐[(2,3,4,5‐tetrahydro‐4‐methylidene‐5‐oxo‐2‐phenylfuran‐2‐yl)methoxy]quinolin‐2(1H)‐one ( 10b ) was the most active against arachidonic acid (AA) induced platelet aggregation with an IC₅₀ of 0.23 μM . For the inhibition of platelet‐activating factor (PAF) induced aggregation, 6‐{[2‐(4‐fluorophenyl)‐2,3,4,5‐tetrahydro‐4‐methylidene‐5‐oxofuran‐2‐yl]methoxy}‐3,4‐dihydroquinolin‐2(1H)‐one ( 9c ) was the most potent with an IC₅₀ value of 1.83 μM .     

Pseudonocardides A – G,New γ‐Butyrolactones from Marine‐derived Pseudonocardia sp. YIM M13669

Seven new γ‐butyrolactones, named pseudonocardides A – G ( 1  –  7 ), were isolated from the marine‐derived actinomycete strain Pseudonocardia sp. YIM M13669. Their structures were elucidated on the basis of spectroscopic data including 1D‐ and 2D‐NMR, and HR‐ESI‐MS. The absolute configuration of 1 was determined by X‐ray crystallographic analysis of 1a (4‐bromobenzoate derivative of 1 ). The antibacterial activity against Mycobacterium smegmatis MC²155 and cytotoxicities of compounds 1  –  7 were evaluated in this study.     

Synthesis and Antitumor Activity Evaluation of γ-Monofluorinated and γ,γ-Difluorinated Goniothalamin Analogues

A series of novel γ,γ‐difluorinated Goniothalamin analogues 4a – 4i and 6a – 6i were synthesized. The key steps included the construction of C‐5 stereocenter adjacent to gem‐difluoromethylene group by way of lipase AK catalyzed kinetic resolution, the introduction of aryl group via Stille coupling, and lactonization by 1,5‐oxidative cyclization. These γ,γ‐difluorinated Goniothalamin analogues 4a – 4i and their enantiomers 6a – 6i , together with several corresponding γ‐monofluorinated Goniothalamin analogues were biologically evaluated against four different cancer cell lines. Compound 7h showed a nearly equivalent potency as the parent (R)‐Goniothalamin in the micromolar range. The different fluorine effects between fluoromethylene and gem‐difluoromethylene on antitumor activity were discussed through the analysis of bioassay data.     

Synthesis and Cytotoxic Evaluation of Some 4‐Anilinofuro[2,3‐b]quinoline Derivatives

Some 4‐anilinofuro[2,3‐b]quinoline derivatives were synthesized from dictamnine, a natural alkaloid, and evaluated for their cytotoxicity in the NCI's full panel of 60 human cancer cell lines derived from nine cancer cell types, including leukemia, non‐small‐cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer. 1‐[4‐(Furo[2,3‐b]quinolin‐4‐ylamino)phenyl]ethanone ( 5 ) (mean GI₅₀=0.025 μM ), bearing an 4‐acetylanilino substituent at C(4) of furo[2,3‐b]quinoline, was more active than its 3‐acetylanilino counterpart 7 (mean GI₅₀=5.27 μM ), and both clinically used anticancer drugs, N‐[4‐(acridin‐9‐ylamino)‐3‐methoxyphenyl]methanesulfonamide (m‐AMSA; mean GI₅₀=0.44 μM ) and daunomycin (mean GI₅₀=0.044 μM ). Compound 5 was capable of inhibiting all types of cancer cells tested with a mean GI₅₀ of less than 0.04 μM in each case except for the non‐small‐cell lung cancer (average GI₅₀=1.75 μM ). Although non‐small‐cell lung cancer is resistant to compound 5 , the sensitivity within this type of cancer cells varies: HOP‐62 (GI₅₀<0.01 μM ), NCI‐H460 (GI₅₀=0.01 μM ), and NCI‐H522 (GI₅₀<0.01 μM ) are very sensitive, while HOP‐92 (GI₅₀ = 12.4 μM ) is resistant. Among these non‐small‐cell lung cancers, NCI‐H522 was found to be very sensitive to 5, 8a , and 8b with a GI₅₀ values of <0.01, 0.074, and <0.01 μM , respectively.     

Antiplatelet α-Methylidene-γ-butyrolactones: Synthesis and evaluation of quinoline,flavone, and xanthone derivatives

As a continuation of our previous studies on the synthesis and antiplatelet activity of coumarin derivatives of α-methylidene-γ-butyrolactones, certain quinoline, flavone, and xanthone derivatives were synthesized and evaluated for antiplatelet activity against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. These compounds were synthesized from quinolin-8-ol, flavon-7-ol, and xanthon-3-ol, respectively, via alkylation and Reformatsky-type condensation (Schemes 1–3). By the comparison with comparison with coumarin α-methylidene-γ-butyrolactone 3a , flavone and xanthone derivatives, 3b and 3c , respectively, are more selective in which only AA- and collagen-induced aggregation are strongly inhibited. Most of the quinoline derivatives ( 9a–e ) exhibited broad-spectrum antiplatelet activities.     

Synthesis and Cytotoxic and Antiplatelet Activities of Dibenzofuran‐ and Carbazole‐Substituted Oximes

The dibenzofuran‐ and carbazole‐substituted oximes or methyloximes 5 – 10 were prepared and evaluated for their cytotoxic and antiplatelet activities. These compounds were synthesized via alkylation of dibenzofuran‐2‐ol or 9H‐carbazol‐2‐ol with α‐halocarbonyl reagents, followed by reaction with NH₂OH or NH₂OMe (Scheme). A preliminary anticancer assay indicated that the oxime‐type dibenzofuran derivatives 5 and 7a – d are active, while the corresponding oxime ethers 9b and 9c are inactive at the same concentration. Therefore, a H‐bond‐donating group seems to be crucial for cytotoxicity. Among the compounds tested, 2‐[(dibenzo[b,d]furan‐2‐yl)oxy]‐1‐(4‐methoxyphenyl)ethan‐1‐one O‐methyloxime ( 9c ) exhibited potent inhibitory activity against platelet aggregation induced by arachidonic acid, with an IC₅₀ value of 14.87 μM , without being cytotoxic at a concentration of 100 μM .     

Xanthones with α‐Glucosidase Inhibitory Activities from Aspergillus versicolor,a Fungal Endophyte of Huperzia serrata

Three new xanthones, namely huperxanthones A–C ( 1 – 3 , resp.), were obtained from the cultures of Aspergillus versicolor, a fungal endophyte of Huperzia serrata, together with 1,7‐dihydroxy‐8‐(methoxycarbonyl)xanthone‐3‐carboxylic acid ( 4 ), β‐diversonolic acid methyl ester ( 5 ), 4‐hydroxyvertixanthone ( 6 ), and sydowinin B ( 7 ). The structures of the new compounds were established by detailed NMR and MS analysis, especially by 2D‐NMR experiments. All xanthones were evaluated for their effects on α‐glucosidase. Compound 4 exhibited a potent inhibitory activity against α‐glucosidase with an IC₅₀ value of 0.24 mM (vs. 0.38 mM for acarbose). The rest of the compounds showed weak or no activity against α‐glucosidase.     

A Convenient Synthesis of 2,3‐Dihydro‐3‐methylidene‐1H‐isoindol‐1‐ones by Reaction of 2‐Formylbenzo­nitriles with Dimethyloxosulfonium Methylide

A facile method for the synthesis of 2,3‐dihydro‐3‐methylidene‐1H‐isoindol‐1‐one and its derivatives carrying substituent(s) at C(5) and/or C(6) has been developed. The reaction of 2‐formylbenzonitrile ( 1a ) with dimethyloxosulfonium methylide, generated by the treatment of trimethylsulfoxonium iodide with NaH in DMSO/THF at 0°, resulted in the formation of 2,3‐dihydro‐3‐methylidene‐1H‐isoindol‐1‐one ( 2a ) in 77% yield. Similarly, six 2‐formylbenzonitriles carrying substituent(s) at C(4) and/or C(5), i.e., 1b – 1g , also gave the corresponding expected products 2b – 2g in comparable yields.     

Design,Synthesis, NMR‐Solution and X‐Ray Crystal Structure of N‐Acyl‐γ‐dipeptide Amides That Form a βII′‐Type Turn

Conformational analysis of γ‐amino acids with substituents in the 2‐position reveals that an N‐acyl‐γ‐dipeptide amide built of two enantiomeric residues of unlike configuration will form a 14‐membered H‐bonded ring, i.e., a γ‐peptidic turn (Figs. 1 – 3). The diastereoselective preparation of the required building blocks was achieved by alkylation of the doubly lithiated N‐Boc‐protected 4‐aminoalkanoates, which, in turn, are readily available from the corresponding (R)‐ or (S)‐α‐amino acids (Scheme 1). Coupling two such γ‐amino acid derivatives gave N‐acetyl and N‐[(tert‐butoxy)carbonyl] (Boc) dipeptide methyl amides ( 1 and 10 , resp.; Fig. 2, Scheme 2); both formed crystals suitable for X‐ray analysis, which confirmed the turn structures in the solid state (Fig. 4 and Table 4). NMR Analysis of the acetyl derivative 1 in CD₃OH, with full chemical‐shift and coupling assignments, and, including a 300‐ms ROESY measurement, revealed that the predicted turn structure is also present in solution (Fig. 5 and Tables 1 – 3). The results described here are yet another piece of evidence for the fact that more stable secondary structures are formed with a decreasing number of residues, and with increasing degree of predictability, as we go from α‐ to β‐ to γ‐peptides. Implications of the superimposable geometries of the actual turn segments (with amide bonds flanked by two quasi‐equatorial substituents) in α‐, β‐, and γ‐peptidic turns are discussed.     

Synthesis of Halogenated α,β‐Unsaturated γ‐Butyrolactone Derivatives by Triphenylphosphine‐Catalyzed Cyclization of α‐Halogeno Ketones with Dialkyl Acetylenedicarboxylates (=Dialkyl But‐2‐ynedioates)

A Ph₃P‐catalyzed cyclization of α‐halogeno ketones 2 with dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) 3 produced halogenated α,β‐unsaturated γ‐butyrolactone derivatives 4 in good yields (Scheme 1, Table). The presence of electron‐withdrawing groups such as halogen atoms at the α‐position of the ketones was necessary in this reaction. Cyclization of α‐chloro ketones resulted in higher yields than that of the corresponding α‐bromo ketones. Dihalogeno ketones similarly afforded the expected γ‐butyrolactone derivatives in high yields.     

Facile Synthesis of 5‐Hexyl‐4‐methyl‐γ‐butyrolactone via Nef Reaction as a Key Step

A racemic cis/trans mixture of 5‐hexyl‐4‐methyl‐γ‐butyrolactone was easily synthesized from 1‐iodoheptane in four steps with inexpensive and readily available reagents. Our new synthesis method can be potentially employed for mass production of the 4‐methyl‐5‐hexyl‐γ‐butyrolactone as well as other poly‐alkyl substituted γ‐butyrolactones.     

Enzyme‐Mediated Preparation of (+)‐ and (−)‐β‐Irone and (+)‐ and (−)‐cis‐γ‐Irone from Irone alpha®

The (−)‐ and (+)‐β‐irones ((−)‐ and (+)‐ 2 , resp.), contaminated with ca. 7 – 9% of the (+)‐ and (−)‐trans‐α‐isomer, respectively, were obtained from racemic α‐irone via the 2,6‐trans‐epoxide (±)‐ 4 (Scheme 2). Relevant steps in the sequence were the LiAlH₄ reduction of the latter, to provide the diastereoisomeric‐4,5‐dihydro‐5‐hydroxy‐trans‐α‐irols (±)‐ 6 and (±)‐ 7 , resolved into the enantiomers by lipase‐PS‐mediated acetylation with vinyl acetate. The enantiomerically pure allylic acetate esters (+)‐ and (−)‐ 8 and (+)‐ and (−)‐ 9 , upon treatment with POCl₃/pyridine, were converted to the β‐irol acetate derivatives (+)‐ and (−)‐ 10 , and (+)‐ and (−)‐ 11 , respectively, eventually providing the desired ketones (+)‐ and (−)‐ 2 by base hydrolysis and MnO₂ oxidation. The 2,6‐cis‐epoxide (±)‐ 5 provided the 4,5‐dihydro‐4‐hydroxy‐cis‐α‐irols (±)‐ 13 and (±)‐ 14 in a 3 : 1 mixture with the isomeric 5‐hydroxy derivatives (±)‐ 15 and (±)‐ 16 on hydride treatment (Scheme 1). The POCl₃/pyridine treatment of the enantiomerically pure allylic acetate esters, obtained by enzymic resolution of (±)‐ 13 and (±)‐ 14 , provided enantiomerically pure cis‐α‐irol acetate esters, from which ketones (+)‐ and (−)‐ 22 were prepared (Scheme 4). The same materials were obtained from the (9S) alcohols (+)‐ 13 and (−)‐ 14 , treated first with MnO₂, then with POCl₃/pyridine (Scheme 4). Conversely, the dehydration with POCl₃/pyridine of the enantiomerically pure 2,6‐cis‐5‐hydroxy derivatives obtained from (±)‐ 15 and (±)‐ 16 gave rise to a mixture in which the γ‐irol acetates 25a and 25b and 26a and 26b prevailed over the α‐ and β‐isomers (Scheme 5). The (+)‐ and (−)‐cis‐γ‐irones ((+)‐ and (−)‐ 3 , resp.) were obtained from the latter mixture by a sequence involving as the key step the photochemical isomerization of the α‐double bond to the γ‐double bond. External panel olfactory evaluation assigned to (+)‐β‐irone ((+)‐ 2 ) and to (−)‐cis‐γ‐irone ((−)‐ 3 ) the strongest character and the possibility to be used as dry‐down note.     

Practical Stereo‐ and Regioselective,Copper(I)‐Promoted Strecker Synthesis of Sugar‐Modified α,β‐Unsaturated Imines

The regio‐ and stereoselective, Lewis acid catalyzed Strecker reaction between Me₃SiCN and different aldimines incorporating a 2,3,4,6‐tetrakis‐O‐pivaloyl‐D ‐glucopyranosyl (Piv₄Glc) chiral auxiliary has been worked out. Depending on the conditions used, high yields (up to 95%) and good diastereoselectivities (de > 86%) were achieved under mild conditions (Table 1), especially with CuBr ? Me₂S as catalyst. Our protocol allows the ready preparation of asymmetric β,γ‐unsaturated α‐amino acids such as (R)‐2‐amino‐4‐phenylbut‐3‐enoic acid ( 13 ; Scheme 2) and congeners thereof.     

Hydrolysis Reaction of N-Phosphoryl-α-, β- and γ-amino Acids Studied by HPLC

The hydrolysis reactions of N-（O,O＇diisopropyl）phosphoryl-L-α-alanine （DIPP-L-α-Ala）, N-（O,O＇diisopropyl）- phosphoryl-D-α-alanine （DIPP-D-α-Ala）, N-（O,O＇-diisopropyl）phosphoryl-β-alanine （DIPP-β-Ala） and N-（O,O＇-diisopropyl）phosphoryl-γ-amino butyric acid （DIPP-γ-Aba）, were studied by HPLC and their hydrolysis reaction kinetic equations were obtained. Under acid conditions, the reaction rate of DIPP-L-α-Ala was close to that of DIPP-D-α-Ala and the same rule was true between DIPP-β-Ala and DIPP-γ-Aba. Meantime, the reaction rate of DIPP-L/D-α-Ala was as 10 times as that of DIPP-β-Ala or DIPP-γ-Aba. Under basic conditions, the hydrolysis reactions of DIPP-β-Ala and DIPP-γ-Aba almost did not take place and the reaction rate of DIPP-L/D-α-Ala was about 1/10 of that under acid conditions. Moreover, theoretical calculation further illuminated the differences of the hydrolysis rate from the view of energy. The results would provide some helpful clues to why nature chose a-amino acids but not other kinds of analogs as protein backbones.     

Synthesis of Some Novel Phenyl Substituted Oxothiazolidin- 1’’,3’’,4’’-thiadiazolo-[3’,4’-b]thiazoline of 3β-Substituted Cholestane

Three title compounds 4a—4c have been synthesized by the cyclodehydration of 1’-benzylidine-4’-(3β-substituted-5α-cholestane-6-yl)thiosemicarbazones 2a—2c with thioglycolic acid followed by the treatment with cold conc. H2SO4 in dioxane. The compounds 2a—2c were prepared by condensation of 3β-substituted-5α-cholestan- 6-one-thiosemicarbazones 1a—1c with benzaldehyde. These thiosemicarbazones 1a—1c were obtained by the reaction of corresponding 3β-substituted-5α-cholestan-6-ones with thiosemicarbazide in the presence of few drops of conc. HCl in methanol. The structures of the products have been established on the basis of their elemental, analytical and spectral data.     

Structural Characterization and Enzymatic Degradation of α‐, β‐, and γ‐Crystalline Forms for Poly(β‐propiolactone)

A structural comparison of three different crystalline forms of poly(β‐propiolactone) (PPL) was carried out by wide‐angle X‐ray diffraction, Fourier‐transform infrared spectroscopy, and differential scanning calorimetry. The α‐form in a hot‐drawn and annealed film represents a 2₁ helix conformation. The β‐form in a cold‐drawn and annealed film represents a planar zigzag conformation. The γ‐form in an oriented sedimented mat of solution‐grown chain‐folded lamellar crystals also implies a planar zigzag conformation. The solution‐cast film depicts similar outlines with the γ‐form in lamellar crystals in all the experimental measurements, suggesting that the molecular chain in the solution‐cast film has a planar zigzag conformation. While elongation at break decreased, tensile strength and Young's modulus increased with an increase in the crystallinity, independent of the crystalline forms. The influence of the enzymatic degradation of these crystal structures has been investigated by using an extracellular PHB depolymerase purified from Ralstonia pickettii T1. The rate of degradation was in the order of β‐form > α‐form > solution‐cast (γ‐form) film, and the different surface morphologies after partial enzymatic degradation were observed in scanning electron micrographs. It is suggested that the crystal structure is one of the important factors for determining the rate of degradation together with crystallinity.

Enzymatic degradation profiles of poly(β‐propiolactone) films.