A novel amide alkaloid, bursatamide A (1), featuring an unprecedented propyl-hexahydronaphthalene carbon framework, was isolated from the infrequently studied sea hare Bursatella leachi, alongside a new 3-phenoxypropanenitrile alkaloid, bursatellin B (2), and twelve known compounds. The structures of 1 and 2 were elucidated through comprehensive spectroscopic data analyses, while their relative and absolute configurations (ACs) were established through total synthesis and a series of quantum chemical calculations, including calculated electronic circular dichroism (ECD) spectra, optical rotatory dispersion (ORD) methods, and DP4+ probability analyses. Bursatamide A (1) demonstrated inhibitory effects against the human pathogenic bacteria Listeria monocytogenes and Vibrio cholerae. Erythro-bursatellin B (21), a diastereoisomer of 2, exhibited notable antibacterial activity against the fish pathogenic bacterium Streptococcus parauberis FP KSP28, with an MIC90 value of 0.0472 μg·mL−1.
| [1] |
Kawamura A, Kita M, Kigoshi H. Aplysiasecosterol A: a 9, 11-Secosteroid with an unprecedented tricyclic γ-diketone structure from the sea hare Aplysia kurodai[J]. Angew Chem Int Ed Engl, 2015, 54(24): 7073-7076.
|
| [2] |
Kicklighter CE, Germann M, Kamio M, et al. Molecular identification of alarm cues in the defensive secretions of the sea hare Aplysia californica[J]. Anim. Behav, 2007, 74: 1481-1492.
|
| [3] |
Kicklighter CE, Kamio M, Nguyen L, et al. Mycosporine-like amino acids are multifunctional molecules in sea hares and their marine community[J]. Proc Natl Acad Sci USA, 2011, 108(28): 11494-11499.
|
| [4] |
Tallita CL Tavares, Vanessa LR Nogueira, et al.Ilka M Vasconcelos, Further characterization and mode of action of dactylomelin-P, an antibacterial protein isolated from the ink of the sea hare Aplysia dactylomela (Rang, 1828)[J]. J Exp Mar Biol Ecol, 2011, 407: 200-206.
|
| [5] |
Alehaideb ZI, Venkatraman A, Kokane M, et al. Bursatella leachii purple ink secretion concentrate exerts cytotoxic properties against human hepatocarcinoma cell line (HepG2): in vitro and in silico studies[J]. Molecules, 2022, 27(3): 826.
|
| [6] |
Mohamed-Elamir FH, Alaa YM, Abou El-Hamd HM, et al. New cytotoxic halogenated sesquiterpenes from the egyptian sea hare, Aplysia oculifera[J]. ChemInform, 2014, 45: 1711.
|
| [7] |
Ohyoshi T, Zhao Y, Kigoshi H. Isolation and synthesis of azuriaplysins A and B, bromoditerpenes with an α-Methylene carbonyl from the sea hare aplysia kurodai[J]. J Nat Prod, 2022, 85(8): 2082-2089.
|
| [8] |
Jiménez-Romero C, González K, Rodríguez AD. Dolabriferols B and C, non-contiguous polypropionate esters from the tropical sea hare Dolabrifera dolabrifera[J]. Tetrahedron Lett, 2012, 53(49): 6641-6645.
|
| [9] |
Suntornchashwej S, Chaichit N, Isobe M, et al. Hectochlorin and morpholine derivatives from the Thai sea hare, Bursatella leachii[J]. J Nat Prod, 2005, 68(6): 951-955.
|
| [10] |
Suntornchashwej S, Suwanborirux K, Koga K, et al. Malyngamide X: the first (7R)-lyngbic acid that connects to a new tripeptide backbone from the Thai sea hare Bursatella leachii[J]. Chem - Asian J, 2007, 2(1): 114-122.
|
| [11] |
Cimino G, Gavagnin M, Sodano G, et al. Revised structure of bursatellin[J]. J Org Chem, 1987, 52(11): 2301-2303.
|
| [12] |
Bailey WF, England MD, Mealy MJ, et al. Facile O-deallylation of allyl ethers via S(N)2' reaction with tert-butyllithium [J]. Org Lett, 2000, 2(4): 489-491.
|
| [13] |
Miyamoto T, Honda M, Sugiyama S, et al. Studies on the constituents of marine Opisthobranchia. III. Isolation and structure of two 5,8α-epidioxysterols and a cholesteryl ester mixture from the albumen gland of Aplysia juliana[J]. Liebigs Ann Chem, 1988, (6): 589.
|
| [14] |
Pereira RB, Pereira DM, Jiménez C, et al. Anti-inflammatory effects of 5α,8α-epidioxycholest-6-en-3β-ol, a steroidal endoperoxide isolated from Aplysia depilans, based on bioguided fractionation and NMR analysis[J]. Mar Drugs, 2019, 17(6): 330.
|
| [15] |
Shen H, Liu X, Jiang M, et al. Anti-inflammatory cembrane-type diterpenoids and prostaglandins from soft coral Lobophytum sarcophytoides[J]. Mar Drugs, 2019, 17(8): 481.
|
| [16] |
Zhang J, Liang Y, Liao XJ, et al. Isolation of a new butenolide from the South China Sea gorgonian coral Subergorgia suberosa[J]. Nat Prod Res, 2014, 28(3): 150-155.
|
| [17] |
Campos PE, Herbette G, Fougere L, et al. An aminopyrimidone and aminoimidazoles alkaloids from the rodrigues calcareous marine sponge Ernsta naturalis[J]. Mar Drugs, 2022, 20(10): 637.
|
| [18] |
Camus P, Lhomme MF, Lhomme J, et al. Modification of guanine bases: reaction of guanine nucleosides with aryl and chlorosulfonyl isocyanates[J]. Tetrahedron Lett, 1989, 30(4): 467.
|
| [19] |
Drenichev M, Alexeev CS, Kurochkin NN, et al. Phosphorylases for the preparation of purine and pyrimidine 2'-deoxynucleosides[J]. Adv Synth Catal, 2018, 360(2): 305-312.
|
| [20] |
Cieslak J, Grajkowski A, Ausin C, et al. Protection of the 2'-hydroxy function of ribonucleosides as an iminooxymethyl propanoate and its 2'-O-deprotection through an intramolecular decarboxylative elimination process[J]. Eur J Org Chem, 2016, 35: 5817-5821.
|
| [21] |
Goody RS, Isakov M. Simple synthesis and separation of the diastereomers of α-thio analogs of ribo- and deoxyribo- di- and triphosphates[J]. Tetrahedron Lett, 1986, 27(31): 3599.
|
| [22] |
Zhou X, Wen K, Yang X, et al. Chemical constituents from the sea urchin Glyptocidaris crenularis. Biochem[J]. Syst Ecol, 2010, 38: 103-105.
|
| [23] |
Wu Q, Li SW, Xu H, et al. Complex Polypropionates from a South China Sea photosynthetic mollusk: isolation and biomimetic synthesis highlighting novel rearrangements[J]. Angew Chem Int Ed Engl, 2020, 59(29): 12105-12112.
|
| [24] |
Mándi A, Kurtán T. Applications of OR/ECD/VCD to the structure elucidation of natural products[J]. Nat Prod Rep, 2019, 36(6): 889-918.
|
| [25] |
Cooper JK, Li K, Aubé J, et al. Application of the DP4 probability method to flexible cyclic peptides with multiple independent stereocenters: the true structure of cyclocinamide A[J]. Org Lett, 2018, 20(14): 4314-4317.
|
| [26] |
Dražić T, Roje M, Jurin M, et al. Synthesis, separation and absolute configuration determination by ECD spectroscopy and TDDFT calculations of 3‐amino‐β‐lactams and derived guanidines[J]. Eur J Org Chem, 2016, 24: 4189-4199.
|
| [27] |
Xu L, Wu P, Wright SJ, et al. Bioactive polycyclic tetramate macrolactams from Lysobacter enzymogenes and their absolute configurations by theoretical ECD calculations[J]. J Nat Prod, 2015, 78(8): 1841-1847.
|
| [28] |
Mamos P, Krokidis MG, Papadas A, et al. On the use of the antibiotic chloramphenicol to target polypeptide chain mimics to the ribosomal exit tunnel[J]. Biochimie, 2013, 95(9): 1765-1772.
|
| [29] |
Racioppi R, Gavagnin M, Strazzullo G, et al. Stereochemistry and synthesis of bursattelin from chloramphenicol[J]. Tetrahedron lett, 1990, 31(4): 573-574.
|
| [30] |
Kristianslund R, Vik A, Hansen TV. A convenient synthesis of phenols[J]. Synth Commun, 2018, 48(21): 2809-2814.
|
| [31] |
Dethe DH, Ranjan A, Pardeshi VH. Asymmetric first total syntheses and assignment of absolute configuration of oxazinin-5, oxazinin-6 and preoxazinin-7[J]. Org Biomol Chem, 2011, 9(23): 7990-7992.
|
| [32] |
Dethe DH, Ranjan A. Enantioselective total syntheses and determination of absolute configuration of marine toxins, oxazinins[J]. RSC Adv, 2013, 3(45): 23692-23703.
|
| [33] |
Morin JB, Sello JK. Efficient synthesis of a peculiar vicinal diamine semiochemical from Streptomyces natalensis[J]. Org Lett, 2010, 12(15): 3522-3524.
|
| [34] |
Liardo E, Ríos-Lombardía N, Morís F, et al. Hybrid organo-and biocatalytic process for the asymmetric transformation of alcohols into amines in aqueous medium[J]. ACS Catal, 2017, 7(7): 4768-4774.
|
| [35] |
Sun LL, Li WS, Li J, et al. Uncommon diterpenoids from the South China Sea soft coral Sinularia humilis and their stereochemistry[J]. J Org Chem, 2021, 86(4): 3367-3376.
|
Funding
National Key Research and Development Program of China(2021YFF0502400)
National Key Research and Development Program of China(2022YFC2804100)
Natural Science Foundation of China(82022069)
Natural Science Foundation of China(42076099)
Shandong Laboratory Program(SYS202205)
“Youth Innovation Promotion Association” of CAS(Y202065)
Fundamental Research Projects of Science & Technology In-novation and development Plan in Yantai City(2023JCYJ057)
CAS Youth Interdisciplinary Team, the Shandong Science and Technology Major Project of Innovation and Entrepreneurship Community with Antibodydrug(E321020)
Youth Fund from Natural Science Foundation of Shandong Province(ZR2023QD162)
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