PMC

Outcome measurement of hyperglycemic events and ketone testing.
Graphs show differences between blood and urine ketone testing groups in numbers of hyperglycemic event (HE)/month (A), numbers of accurate ketone tests/month (B), numbers of missed ketone tests/month (C), numbers of inaccurate ketone tests/month (D), percentage of positive ketone tests during accurate testing (E) and percentage of positive ketone tests during inaccurate testing (F). Blood ketone testing group (group A) is shown in red and urine ketone testing group (group B) is shown in orange. ^*p < 0.05 compared blood versus urine ketone testing.

Ketone 3a can be synthesized from ketone 1 in two steps by selective deketalization with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and subsequent acetylation with Ac₂O and catalytic amount (2 mol%) of DMAP (). Ketone 3a is highly electrophilic and can easily form a hydrate with water. With this method, ketone 3a can be obtained largely in ketone form by avoiding moisture. The β-acetate of ketone 3a is prone to elimination to form an enone. To minimize this elimination, it is crucial to use only a small amount of DMAP (ca. 2 mol%) and to carefully control the reaction time in the acetylation step. Nevertheless, it was found that the resulting enone was barely active and had little impact on the asymmetric epoxidation. Alternatively, ketone 3a can be readily prepared in hydrate form from ketone 1 by one pot deketalization and acetylation with ZnCl₂, AcOH, and Ac₂O in water ().,, However, if ketone 3a is desired, it can be obtained from 3a·H₂O by simply dissolving 3a·H₂O in solvents such as EtOAc and stirring with Na₂SO₄ overnight at rt, followed by filtration and concentration or by passing 3a·H₂O through a short column of SiO₂. In CDCl₃, the hydrate gradually converted into the ketone as judged by ¹H NMR (25% ketone at 10 min, 50% ketone at 30 min, 67% ketone at 1 h, 90% ketone at 2 h, 100% ketone at 11 h). In CD₃CN-D₂O (1.5:1, v/v), ca. 21% of the ketone was formed from the hydrate at 1 h (ca. 22% at 7 h). When the ketone was subjected to the same solvent mixture, ca. 26% of the ketone remained at 1 h (ca. 25% at 7 h). It appears that a similar amount of the ketone was present at around 1 h regardless of whether the ketone or its hydrate was used. Similar conversions and ee’s were also obtained for the epoxidation with ethyl trans-cinnamate as test substrate when either the ketone or its hydrate was used. In addition to ketone 3a, several analogues including diesters 3b–e and 6, as well as mono-ester ketones 5, 7, and 10 were also prepared for the epoxidation studies ( and ).

Ketone 3a can be synthesized from ketone 1 in two steps by selective deketalization with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and subsequent acetylation with Ac₂O and catalytic amount (2 mol%) of DMAP (). Ketone 3a is highly electrophilic and can easily form a hydrate with water. With this method, ketone 3a can be obtained largely in ketone form by avoiding moisture. The β-acetate of ketone 3a is prone to elimination to form an enone. To minimize this elimination, it is crucial to use only a small amount of DMAP (ca. 2 mol%) and to carefully control the reaction time in the acetylation step. Nevertheless, it was found that the resulting enone was barely active and had little impact on the asymmetric epoxidation. Alternatively, ketone 3a can be readily prepared in hydrate form from ketone 1 by one pot deketalization and acetylation with ZnCl₂, AcOH, and Ac₂O in water ().,, However, if ketone 3a is desired, it can be obtained from 3a·H₂O by simply dissolving 3a·H₂O in solvents such as EtOAc and stirring with Na₂SO₄ overnight at rt, followed by filtration and concentration or by passing 3a·H₂O through a short column of SiO₂. In CDCl₃, the hydrate gradually converted into the ketone as judged by ¹H NMR (25% ketone at 10 min, 50% ketone at 30 min, 67% ketone at 1 h, 90% ketone at 2 h, 100% ketone at 11 h). In CD₃CN-D₂O (1.5:1, v/v), ca. 21% of the ketone was formed from the hydrate at 1 h (ca. 22% at 7 h). When the ketone was subjected to the same solvent mixture, ca. 26% of the ketone remained at 1 h (ca. 25% at 7 h). It appears that a similar amount of the ketone was present at around 1 h regardless of whether the ketone or its hydrate was used. Similar conversions and ee’s were also obtained for the epoxidation with ethyl trans-cinnamate as test substrate when either the ketone or its hydrate was used. In addition to ketone 3a, several analogues including diesters 3b–e and 6, as well as mono-ester ketones 5, 7, and 10 were also prepared for the epoxidation studies ( and ).

Ketone 3a can be synthesized from ketone 1 in two steps by selective deketalization with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and subsequent acetylation with Ac₂O and catalytic amount (2 mol%) of DMAP (). Ketone 3a is highly electrophilic and can easily form a hydrate with water. With this method, ketone 3a can be obtained largely in ketone form by avoiding moisture. The β-acetate of ketone 3a is prone to elimination to form an enone. To minimize this elimination, it is crucial to use only a small amount of DMAP (ca. 2 mol%) and to carefully control the reaction time in the acetylation step. Nevertheless, it was found that the resulting enone was barely active and had little impact on the asymmetric epoxidation. Alternatively, ketone 3a can be readily prepared in hydrate form from ketone 1 by one pot deketalization and acetylation with ZnCl₂, AcOH, and Ac₂O in water ().,, However, if ketone 3a is desired, it can be obtained from 3a·H₂O by simply dissolving 3a·H₂O in solvents such as EtOAc and stirring with Na₂SO₄ overnight at rt, followed by filtration and concentration or by passing 3a·H₂O through a short column of SiO₂. In CDCl₃, the hydrate gradually converted into the ketone as judged by ¹H NMR (25% ketone at 10 min, 50% ketone at 30 min, 67% ketone at 1 h, 90% ketone at 2 h, 100% ketone at 11 h). In CD₃CN-D₂O (1.5:1, v/v), ca. 21% of the ketone was formed from the hydrate at 1 h (ca. 22% at 7 h). When the ketone was subjected to the same solvent mixture, ca. 26% of the ketone remained at 1 h (ca. 25% at 7 h). It appears that a similar amount of the ketone was present at around 1 h regardless of whether the ketone or its hydrate was used. Similar conversions and ee’s were also obtained for the epoxidation with ethyl trans-cinnamate as test substrate when either the ketone or its hydrate was used. In addition to ketone 3a, several analogues including diesters 3b–e and 6, as well as mono-ester ketones 5, 7, and 10 were also prepared for the epoxidation studies ( and ).