mPEG-PLLA from PolySciTech used for synthesis of photodynamic chemotherapy agent

Photodynamic therapy is a novel cancer treatment option which utilizes special agents, referred to as photosensitizers. These reagents are inactive and non-toxic under typical conditions but can be activated by certain wavelengths of light to kill cancerous cells. The benefit of such a therapy, over conventional chemotherapy, is that the location of action can be controlled by selectively illuminating the tumor region. PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide variety of block copolymers which work well for forming micelle or nanoparticle formulations for medicinal delivery. Recently, mPEG-PLLA (PolyVivo AK004) was utilized by researchers at Wroclaw University as a precursor to synthesize zinc(II) phthalocyanine conjugate for photodynamic therapy. This research holds promise for safe and effective cancer therapy with lower side-effects. Read more: Lamch, Łukasz, Marta Tsirigotis-Maniecka, Julita Kulbacka, and Kazimiera A. Wilka. “Synthesis of new zinc (II) phthalocyanine conjugates with block copolymers for cancer therapy.” Organic Chemistry part ii (2017): 433-445. http://www.arkat-usa.org/get-file/58826/

“Abstract: Synthetic routes towards new conjugates of hydrophilic zinc(II) phthalocyanine (ZnPc) with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (Pluronic P123) and poly(L-lactide) (PLLA), are described. The main semiproduct ZnPc was obtained by heating 4-nitrophthalimide with urea and zinc chloride, followed by the reduction step. Steglich esterification was used to synthesize two ZnPc-conjugated block copolymers, further utilized in fabrication of polymeric micelles (PMs) – functionalized with the zinc(II) phthalocyanine-type moiety. Biological evaluation of the PMs indicated an acceptable biocompatibility level in accord with requirements in the field of nanotheranostics and nanomedicine. Keywords: ZnPc-conjugated block copolymers; cyclotetramerization; Steglich esterification; fluorescent polymeric micelles; diagnostic marker; in vitro biological evaluation”

Uses for Akanocure Stereotetrad Lactones 5b: Full Lactone Reductions

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One potential usage is the full reduction of the lactone. This reaction has been utilized in the past to provide for synthesis of (+)-neopeltolide fragments, a chemotherapeutic agent. This research holds promise for improved availability of chemotherapeutic agents. Read more: Mineeva, I. “New approach to the synthesis of macrocyclic core of cytotoxic lactone (+)-neopeltolide. Synthesis of CC segment basing on cyclopropanol intermediates.” Russian Journal of Organic Chemistry 51, no. 8 (2015). http://link.springer.com/article/10.1134/S1070428015080023

“A new retrosynthetic procedure was developed for the synthesis of the macrocyclic core of a cytotoxic lactone (+)-neopeltolide utilizing cyclopropanol intermediates. The synthesis was suggested and carried out of the C7–C16 segment of (+)-neopeltolide to obtain (4S,6S)-6-[(2S)-2-hydroxypentyl]-4-methyltetrahydro-2H-pyran-2-one. The possibility was demonstrated of a formal synthesis based on the obtained product of the potential antitumor pharmaceutical (+)-neopeltolide.”

 

Uses for Akanocure Stereotetrad Lactones 5a: Full Lactone Reductions

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One potential usage is the full reduction of the lactone. This reaction has been utilized in the past to provide for synthesis of salinomycin, a powerful antibiotic agent which has proven itself effective against problematic bacterial such as MRSA. This research holds promise for improved antibiotics production. Read more: Yadav, J. S., Vinay K. Singh, and P. Srihari. “Formation of Substituted Tetrahydropyrans through Oxetane Ring Opening: Application to the Synthesis of C1–C17 Fragment of Salinomycin.” Organic letters 16, no. 3 (2014): 836-839. http://pubs.acs.org/doi/abs/10.1021/ol403604u?journalCode=orlef7&quickLinkVolume=16&quickLinkPage=836&selectedTab=citation&volume=16

“The stereoselective synthesis of C1–C17 fragment of salinomycin is achieved. The strategy employs a desymmetrization approach and utilizes an intramolecular oxetane opening reaction with O-nucleophile to result in the tetrahydropyran skeleton as the key step.”

Uses for Akanocure Stereotetrad Lactones 4: lactone openings with sulfur nucleophiles

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One potential reaction is the ring-opening of the lactone using sulfur (thiol) nucleophiles. Recently, this reaction has been applied to the synthesis of peloruside A, a potent chemotherapeutic agent. This research holds promise for improved availability of advanced chemotherapeutic agents. Read more: Raghavan, Sadagopan, and V. Vinoth Kumar. “A stereoselective synthesis of the C9–C19 subunit of (+)-peloruside A.” Organic & biomolecular chemistry 11, no. 17 (2013): 2847-2858. http://pubs.rsc.org/en/content/articlelanding/2013/ob/c3ob27508f#!divAbstract

“Abstract: The stereoselective synthesis of a C9–C19 fragment of the potent antitumor agent peloruside A is disclosed. The C11 stereogenic centre was created by a vinylogous Mukaiyama aldol reaction following Carreira’s protocol, with excellent stereocontrol. The C13 stereogenic centre was introduced by a substrate controlled reduction. The C15 stereocentre was fashioned using Noyori’s asymmetric transfer hydrogenation while the Z-trisubstituted double bond was formed by a regioselective hydrostannation of an alkyne followed by methylation of the resultant vinyl stannane using Lipshutz’s protocol. The C18 chiral centre was introduced by a chemoenzymatic route.”

Uses for Akanocure Stereotetrad Lactones 3: lactone openings with secondary nitrogen nucleophiles

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. These lactones can be ring-opened using secondary nitrogens as the nucleophilic agent. Previously, this reaction has been used to synthesize portions of Aplyronine A, a potent, chemotherapeutic marine macrolide. This research holds promise for enhanced synthesis of difficult-to-source chemotherapy agents. Read more: Hong, Wan Pyo, Mohammad N. Noshi, Ahmad El-Awa, and Philip L. Fuchs. “Synthesis of the C1–C20 and C15–C27 Segments of Aplyronine A.” Organic letters 13, no. 24 (2011): 6342-6345. http://pubs.acs.org/doi/abs/10.1021/ol2024746

“Abstract: The synthesis of C1–C20 and C15–C27 segments of Aplyronine A is described. Oxidative cleavage of cyclic vinyl sulfones has been used to prepare key fragments of Aplyronine A. Key precursors are united by Horner–Wadsworth–Emmons and Julia–Kociensky olefination for the respective elaboration of the C1–C20 and C15–C27 segments.”

Uses for Akanocure Stereotetrad Lactones 2b: lactone openings with primary nitrogen nucleophiles

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One usage is opening the lactone ring utilizing primary nitrogens (amines). This method has been utilized to generate rhizopodin, a myxobacterial metabolite which is a potent actin-binding chemotherapeutic agent. This research holds promise for improved availability of effective chemotherapy agents. Read more: Dieckmann, Michael, Manuel Kretschmer, Pengfei Li, Sven Rudolph, Daniel Herkommer, and Dirk Menche. “Total synthesis of rhizopodin.” Angewandte Chemie International Edition 51, no. 23 (2012): 5667-5670. http://onlinelibrary.wiley.com/doi/10.1002/anie.201301978/full

“The total synthesis of the myxobacterial metabolite rhizopodin, a potent actin-binding anticancer agent, has been achieved. The modular synthesis utilizes a common C1–C22 monomeric unit to assemble the dimeric 38-membered macrodiolide core, which was elaborated by a bidirectional boron-mediated aldol reaction to install the characteristic side-chains. The final global deprotection was critically dependent on the correct choice of silyl protecting groups at C16/C16′.”

Uses for Akanocure Stereotetrad Lactones 2a: lactone openings with primary nitrogen nucleophiles

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One usage is opening the lactone ring utilizing primary nitrogens (amines). For example, these can be utilized to generate aldonamides, a class of widely applicable precursors in and of themselves. You can read more about this application here: Metta-Magaña, Alejandro J., Reyna Reyes-Martínez, and Hugo Tlahuext. “Crystal structure and NMR spectroscopy of aldonamides derived from d-glycero-d-gulo-heptono-1, 4-lactone.” Carbohydrate research 342, no. 2 (2007): 243-253. http://www.sciencedirect.com/science/article/pii/S0008621506005325

“Abstract: We report the preparation of 12 aldonamides derived from d-glycero-d-gulo-heptono-1,4-lactone, their NMR characterization and study (13C, 1H, 15N NMR) in Me2SO-d6 solution. The evaluation of the coupling constants 3JH,H has shown that the sugar chain conformation in solution is all-trans for the studied amides. Because some amides crystallized, we discussed the crystal packing and found motifs. The conformation of the amides in the crystal structures displays two sickles at C2 and C3, with the exception of one that is all-trans. The bends cause the formation of the mean planes C1–C2–C3 and C3–C4–C5–C6–C7 with an average interplanar angle of 88°. We found three main kinds of crystal packing depending on the N-substituent; head-to-tail, bilayer and pseudo-hexagonal mode, all the three show hydrogen-bonding networks that stabilize the crystal lattice. Keywords: Aldonamides; Conformation; 15N NMR; Crystal packing; Hydrogen bonding”

Uses for Akanocure Stereotetrad Lactones 1b: lactone openings with oxygen nucleophiles

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One of the uses is to open the lactone ring utilizing an oxygen nucleophile. This reaction has been successfully applied towards the generation of (+)-Neopeltolide, a promising cytostatic, anti-proliferative macrolide which has a broad range of activity against cancerous cells. The chemical was originally isolated from a deep-water sponges and is very difficult to source naturally in usable quantities. This research usage holds promise for commercial scale synthesis of chemotherapeutic reagents that are difficult to extract from natural resources. You can read more about this application here: Guinchard, Xavier, and Emmanuel Roulland. “Total synthesis of the antiproliferative macrolide (+)-neopeltolide.” Organic letters 11, no. 20 (2009): 4700-4703. http://pubs.acs.org/doi/abs/10.1021/ol902047z?journalCode=orlef7&quickLinkVolume=11&quickLinkPage=4700&selectedTab=citation&volume=11

“A concise total synthesis of the very promising antiproliferative macrolide (+)-neopeltolide (1) has been performed in 16 steps. The main steps of this approach are a RuII-catalyzed alkyne−enal coupling, a Pd0-catalyzed desulfurative cross-coupling, and a stereoselective InIII-catalyzed propargylation. Four stereogenic centers out of six have been set thanks to substrate-controlled diastereoselective reactions with minimal reliance on protecting groups.”

Uses for Akanocure Stereotetrad Lactones 1a: lactone openings with oxygen nucleophiles

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscite…/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One of the uses is to open the lactone ring utilizing an oxygen nucleophile. This synthetic route has previously been used to generate peloruside A, a non-taxoid-site microtubule-stabilizing agent which has promise for chemotherapeutic actions similar to that of paclitaxel. This research usage holds promise for commercial scale synthesis of chemotherapeutic reagents that are difficult to extract from natural resources. You can read more about this application here: Hoye, Thomas R., Junha Jeon, Lucas C. Kopel, Troy D. Ryba, Manomi A. Tennakoon, and Yini Wang. “Total Synthesis of Peloruside A through Kinetic Lactonization and Relay Ring‐Closing Metathesis Cyclization Reactions.” Angewandte Chemie International Edition 49, no. 35 (2010): 6151-6155. http://onlinelibrary.wiley.com/…/10.1002/anie.201002293/full
“Abstract: A convergent total synthesis of peloruside A (1) is described. The key strategic features are a diastereoselective lactonization to generate a C5–C9 valerolactone from the C2-symmetric ketone 3, and a relay ring-closing metathesis reaction to produce a dehydrovalerolactone 2. A new isomer of 1, the valerolactone isopeloruside A (iso-1), was identified. MOM=methoxymethyl.”

Stereotetrad lactone precursors from Akanocure Pharmaceuticals now available through Akina, Inc.

The PolySciTech division of Akina, Inc. (www.polyscitech.com) strives to provide unique and hard-to-find research reagents.  Thanks to a distribution arrangement with Akanocure Pharmacueticals, a Purdue University spin-off company which focuses on finding synthetic routes for hard-to-obtain nature-based pharmaceutical ingredients, we are now distributing stereospecific precursors for generation of polypriopionate medicines. You can see more details about these exciting materials here (https://akinainc.com/polyscitech/products/akanocure/index.php).  These chemicals represent an exciting class of novel therapeutic compounds within the polyketide family. You can learn more about this class of materials and their therapeutic potential in a recent review article: Koskinen, Ari MP, and Kaisa Karisalmi. “Polyketide stereotetrads in natural products.” Chemical Society Reviews 34, no. 8 (2005): 677-690. https://www.researchgate.net/profile/Ari_Koskinen/publication/7577323_Polyketide_Stereotetrads_in_Natural_Products/links/09e4150252cfc302d8000000.pdf

“Abstract: Natural products (or secondary metabolites) remain as the most important source for discovery of new and potential drug molecules. With high resolution data of their structures, and the advancement of synthesis possibilities, analysis of the natural products based on their specific structural features is valuable to those entering the field. In this tutorial review we attempt such an analysis indicating the salient features of the structural classes with examples of the synthesis of each one of them. As the particular class of natural products, we have chosen polyketides.”