Means for sequential solid phase organic synthesis and methods using the same
First Claim
1. A means for carrying out a sequential, solid phase organic synthesis to form a reaction product containing a plurality of reacted subunits comprising an immersible mesh packet having enclosed therein a free form aliquot of reactive particles, said particles being of a size that is larger than any of the foraminae defined by said mesh packet and having a known amount of organic synthesis reactive functionality covalently linked to said particles, said reactive functionality being capable of reacting during said organic synthesis, said mesh packet and said particles being substantially insoluble in water and in organic solvents.
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Abstract
A means for carrying out sequential, solid phase syntheses is disclosed as are methods of its use. The synthesis means comprises a foraminous container that encloses reactive particles. The particles are larger than any of the foraminae and have a known amount of covalently linked organic synthesis reactive functionality that is capable of reacting during the organic syntheses. The container and particles are substantially insoluble in water.
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Citations
40 Claims
- 1. A means for carrying out a sequential, solid phase organic synthesis to form a reaction product containing a plurality of reacted subunits comprising an immersible mesh packet having enclosed therein a free form aliquot of reactive particles, said particles being of a size that is larger than any of the foraminae defined by said mesh packet and having a known amount of organic synthesis reactive functionality covalently linked to said particles, said reactive functionality being capable of reacting during said organic synthesis, said mesh packet and said particles being substantially insoluble in water and in organic solvents.
- 11. A means for carrying out a solid phase organic synthesis to form a reaction product containing a plurality of reacted subunits comprising an immersible mesh packet having enclosed therein a free form aliquot of solid support particles, said particles being of a size that is larger than any of the foraminae defined by said container and being linked to a known amount of identical organic synthesis subunits by selectively severable covalent bonds, each of said subunits containing a functional group capable of reacting during said organic synthesis, but that is protected from so reacting by a selectively removable covalently linked protecting group, said packet and said particles being substantially insoluble in water and organic solvents and being non-reactive with hydrogen fluoride.
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20. A method of carrying out an organic solid phase synthesis to form a reaction product containing a plurality of desired reacted subunits comprising the steps of:
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(a) providing a solid phase organic synthesis means comprising an immersible mesh packet having enclosed therein a free form aliquot of reactive particles, said particles being of a size that is larger than any of the foraminae defined by the mesh packet and having a known amount of organic synthesis reactive functionality covalently linked to said particles, said reactive functionality being capable of reacting during said organic synthesis, said packet and said particles being substantially insoluble in water and organic solvents; (b) immersing said mesh packet in a liquid reaction medium containing first subunits and reacting the first subunits with said reactive functionalities to form within the immersed packet a selectively severable covalent bond between said first subunits and said particles, and to form a synthesis means containing particle-linked subunits, said first subunits including a first functional group that reacts with said reactive functionality and a second reactive functional group capable of reacting during said reaction, but that is protected from reaction by a selectively removable, covalently linked protection group; (c) removing said protecting group from said second reactive functional group while said packet is immersed in a liquid medium to form a synthesis means containing particle-linked subunits having free reactive functional groups; (d) admixing with the synthesis means containing particle-linked subunits having free reactive functional groups, while said packet is immersed in a liquid medium, an excess of identical, known other subunits that contain (i) a functional group capable of reacting with the free reactive groups of said particle-linked subunits and (ii) a second reactive functional group capable of reacting during the organic synthesis, but that is protected from so reacting by a selectively removable covalently linked protecting group; (e) reacting said free reactive groups and said admixed functional groups, while said packet is immersed in a liquid medium, to form covalent bonds, couple the subunit to the particle and form particle-linked subunit reaction products; (f) separating unreacted subunits from said particle-linked reaction products; (g) removing the protecting groups of the coupled subunits of step (d), while said packet is immersed in a liquid medium, to form particle-linked reaction products containing free reactive functional groups; (h) thereafter, serially repeating steps (d), (e), (f) and (g) until particle-linked reaction products containing the desired numer and identity of reacted subunits are synthesized; (i) severing said selectively severable bond between said first subunit and said particle to form a mixture of severed, free reaction products and reacted particles; (j) separating said severed, free reaction products from said reacted particles; and (k) recovering said severed reaction products. - View Dependent Claims (21, 22, 23)
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24. A method of carrying out an organic solid phase synthesis to form a reaction product containing a plurality of desired reacted subunits comprising the steps of:
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(a) providing a solid phase organic synthesis means comprising an immersible mesh packet having enclosed therein a known quantity of resin particles having a known amount of a selectively severable, covalently linked identical organic synthesis subunits that include a selectively removable protecting group covalently bonded to a reactive functional group, said resin particles being of a size that is larger than any of the foraminae defined by said mesh packet, said packet and said particles being substantially insoluble in water and organic solvents and non-reactive with hydrofluoric acid; (b) immersing said mesh packet in a liquid reaction medium for removal of said protecting group and selectively removing said protecting group to form within the immersed packet a synthesis means containing resin-linked subunits having a free reactive group; (c) admixing, while said packet is immersed in a liquid medium, an excess of identical subunits that contain (i) a second reactive functional group capable of reacting with the free reactive groups of said resin-linked subunits, and (ii) another reactive functional group that is capable of reacting during said organic synthesis, but that is protected from so reacting by a selectively removable, covalently bonded protecting group; (d) reacting said free reactive groups and said second reactive groups, while said packet is immersed in a liquid medium, to form covalent bonds, couple said admixed subunit to the resin and form resin-linked reaction products; (e) separating unreacted subunits from said resin-linked reaction products; (f) selectively removing the protecting groups said coupled subunits of step (c), while said packet is immersed in a liquid medium, to form resin-linked reaction products containing free reactive functional groups; (g) thereafter, serially repeating steps (c), (d), (e) and (f) until resin-linked reaction products containing the desired number of reacted subunits are synthesized; (h) severing said selectively severable bond between said first-named subunits and said resin to form free reaction products and reacted particles; (i) separating said free reaction products from said reacted particles; and (j) recovering said severed reaction products. - View Dependent Claims (25, 26, 27, 28)
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29. A method for simultaneously adding a subunit to each of a pluraltiy of resin particle-linked subunits in an organic solid phase synthesis comprising the steps of:
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(a) providing a pluraltiy of synthesis means each of which comprises an immersible mesh packet having enclosed therein a known quantity of particles, said particles being of a size that is larger than any of the foraminae defined by said mesh packet and having a known amount of an organic synthesis subunit covalently linked to said particles by selectively severable bonds, the subunit distal to the particle/subunit link containing a reaction functional group capable of reacting during said organic synthesis, but that is protected from so reacting by a selectively removable covalently bonded protecting group, said packet and said particles being substantially insoluble in water and organic solvents; (b) immersing each said mesh packet in a liquid reaction medium for removal of said protecting group and selectively removing said protecting group from said particle-linked subunits in each of said synthesis means to form an admixture containing a plurality of synthesis means containing particle-linked subunits having free reactive groups; (c) immersing said synthesis means in a liquid medium containing an excess of identical subunits each of which contains (i) a second reactive functional group capable of reacting with the free reactive group of another reactive functional group that is capable of reacting said particle-linked subunits and (ii) another reactive functional group that is capable of reacting during said organic synthesis, but that is protected from so reacting by a selectively removable, covalently bonded protecting group; (d) froming covalent bonds between said free reactive groups and said second reactive group, while said packet is immersed, to couple said admixed subunits to said particles and form a plurality of synthesis means that contain particle-linked reaction products whose distal subunits contain selectively removable, protected reactive functional groups; (e) separating said admixed, unreacted subunits from said particle-linked reaction products; and (f) thereafter separating said plurality of synthesis means from each other. - View Dependent Claims (30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40)
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Specification