British No.5 Liam Broady followed top seed Gael Monfils out of the Viking International at Eastbourne after losing in straight sets to Australia’s Alex de Minaur.
The wildcard, who beat American Frances Tiafoe in the first round, had an early break chance in the second game, but De Minaur held.
World No.18 De Minaur then forced a break, having been 30-0 down, to lead 4-3 which he backed up before keeping pressure on Broady’s serve again to claim another break and take the opening set in 45 minutes.
Broady, ranked 144 in the world, had two more early break chances in the first game of the second set, but could not capitalise as the 22-year-old Australian completed a 6-3 6-4 victory.
Earlier at Devonshire Park, 2017 finalist Monfils slipped to an unexpected defeat in three sets to another Australian, Max Purcell.
Lucky loser Purcell fought back to take the deciding set against the World No.16 and progress 6-4 7-5 6-4.
“It feels unbelievable,” Purcell said. “I’ve struggled to get into any singles events over the past nine months and primarily played doubles, so to get on a run here, on my favourite surface, is great.”
Purcell will next face Andreas Seppi, who defeated Emil Ruusuvuori of Finland 6-2 6-3.
Third seed Lorenzo Sonego moved into the quarter-finals with a 6-4 6-2 win over Australia’s John Millman but Alejandro Davidovich Fokina, the sixth seed, retired with a back problem to hand Vasek Pospisil a quarter-final tie against De Minaur.
No.8 seed Alexander Bublik beat Egor Gerasimov 6-2 6-2 and goes on to meet Italian Sonego for a place in the semi-finals.
Qualifier Ilya Ivashka continued his run with a battling 6-7 (5) 7-5 6-3 win over Australian Alexei Popyrin, while Hungary’s Marton Fucsovics lost in three sets to Soonwoo Kwon.
In the WTA Tour event, top seed Aryna Sabalenka coasted past American Alison Riske 6-1 6-4 to reach the quarter-finals.
However, it proved to be a difficult day for the other leading players.
Second seed Elina Svitolina is out after a 6-4 7-6 (3) defeat by Kazakh player Elena Rybakina, in only the fourth grass-court tournament of the 22-year-old’s career.
Anett Kontaveit ended the hopes of third seed Bianca Andreescu, the Estonian winning 6-3 6-3 against the World No.7
Swiss qualifier Viktorija Golubic recorded a 6-4 6-4 win over compatriot and sixth seed Belinda Bencic, who had reached the final in Berlin last week.
American teenager Coco Gauff was beaten in three sets by Latvian Anastasija Sevastova, the lucky loser progressing 4-6 7-5 6-2.